Datasets:

EMBO
/

SourceData

<article doi="10.1016/j.cmet.2013.04.014" abstract="Mutations in the glucocerebrosidase (gba) gene cause Gaucher disease (GD), the most common lysosomal storage disorder, and increase susceptibility to Parkinson's disease (PD). While the clinical and pathological features of idiopathic PD and PD related to gba (PD-GBA) mutations are very similar, cellular mechanisms underlying neurodegeneration in each are unclear. Using a mouse model of neuronopathic GD, we show that autophagic machinery and proteasomal machinery are defective in neurons and astrocytes lacking gba. Markers of neurodegeneration--p62/SQSTM1, ubiquitinated proteins, and insoluble α-synuclein--accumulate. Mitochondria were dysfunctional and fragmented, with impaired respiration, reduced respiratory chain complex activities, and a decreased potential maintained by reversal of the ATP synthase. Thus a primary lysosomal defect causes accumulation of dysfunctional mitochondria as a result of impaired autophagy and dysfunctional proteasomal pathways. These data provide conclusive evidence for mitochondrial dysfunction in GD and provide insight into the pathogenesis of PD and PD-GBA."><fig id="4677"><title></title><label>Figure 1</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4677"/><sd-panel panel_id="14499">(A) Autophagic markers from mixed <sd-tag id="sdTag1" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> <sd-tag id="sdTag2" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag4" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag5" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− cultures were analyzed via <sd-tag id="sdTag3" source="sdapi" category="assay" entity_type="" role="" text="western blotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">western blotting</sd-tag> using antibodies as indicated.<graphic href="https://api.sourcedata.io/file.php?panel_id=14499"/></sd-panel><sd-panel panel_id="14500">(B) Autophagic flux was analyzed in <sd-tag id="sdTag20" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag21" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag22" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> <sd-tag id="sdTag11" source="sdapi" category="entity" entity_type="cell_type" role="component" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag>. <sd-tag id="sdTag16" source="sdapi" category="entity" entity_type="cell_type" role="component" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> were treated with 100 nM <sd-tag id="sdTag12" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A1</sd-tag> and 1 μM <sd-tag id="sdTag13" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="rapamycin" ext_ids="CHEBI:9168" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="sirolimus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">rapamycin</sd-tag> and flux assayed by comparing <sd-tag id="sdTag14" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>I and <sd-tag id="sdTag15" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>II levels via <sd-tag id="sdTag23" source="sdapi" category="assay" entity_type="" role="" text="western blotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">western blotting</sd-tag>. <sd-tag id="sdTag17" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="β-actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">β-actin</sd-tag> was used as a loading control.(C) Densitometry analyzes of autophagy of (B) expressed as a ratio of <sd-tag id="sdTag18" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>II/<sd-tag id="sdTag19" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>I. Error bars, ± SEM. *p < 0.05.<graphic href="https://api.sourcedata.io/file.php?panel_id=14500"/></sd-panel><sd-panel panel_id="14501">(D) Accumulation of <sd-tag id="sdTag25" source="sdapi" category="entity" entity_type="protein" role="assayed" text="p62" ext_ids="Q64337" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Sqstm1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">p62</sd-tag>/<sd-tag id="sdTag26" source="sdapi" category="entity" entity_type="protein" role="assayed" text="SQSTM1" ext_ids="Q64337" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Sqstm1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">SQSTM1</sd-tag> was analyzed via <sd-tag id="sdTag27" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag>. <sd-tag id="sdTag28" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="β-actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">β-actin</sd-tag> was used as a loading control.<graphic href="https://api.sourcedata.io/file.php?panel_id=14501"/></sd-panel><sd-panel panel_id="14502">(E) <sd-tag id="sdTag32" source="sdapi" category="entity" entity_type="tissue" role="component" text="Midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">Midbrain</sd-tag> <sd-tag id="sdTag36" source="sdapi" category="entity" entity_type="cell_type" role="component" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag> were treated with either 10 μM <sd-tag id="sdTag33" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="MG132" ext_ids="CHEBI:75142" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">MG132</sd-tag> or vehicle control <sd-tag id="sdTag34" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:28262" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="dimethyl sulfoxide" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag>. Proteins were extracted and analyzed via <sd-tag id="sdTag37" source="sdapi" category="assay" entity_type="" role="" text="western blotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">western blotting</sd-tag> and stained with anti-<sd-tag id="sdTag35" source="sdapi" category="entity" entity_type="protein" role="assayed" text="ubiquitin" ext_ids="P62983///P62984///P0CG50///P0CG49" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="Rps27a///Uba52///Ubc///Ubb" ext_tax_ids="10090///10090///10090///10090" ext_tax_names="Mus musculus///Mus musculus///Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">ubiquitin</sd-tag> antibodies.<graphic href="https://api.sourcedata.io/file.php?panel_id=14502"/></sd-panel><sd-panel panel_id="14503">(F) <sd-tag id="sdTag40" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Ubiquitin" ext_ids="P62984///P62983///P0CG50///P0CG49" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="Uba52///Rps27a///Ubc///Ubb" ext_tax_ids="10090///10090///10090///10090" ext_tax_names="Mus musculus///Mus musculus///Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Ubiquitin</sd-tag> linkage of isolated <sd-tag id="sdTag41" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> analyzed using <sd-tag id="sdTag42" source="sdapi" category="assay" entity_type="" role="" text="western blotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">western blotting</sd-tag> with antibodies as indicated. <sd-tag id="sdTag43" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="β-actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">β-actin</sd-tag> was used as a loading control.<graphic href="https://api.sourcedata.io/file.php?panel_id=14503"/></sd-panel><sd-panel panel_id="14504">(G) Proteasomal activity (<sd-tag id="sdTag46" source="sdapi" category="entity" entity_type="protein" role="assayed" text="chymotrypsin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">chymotrypsin</sd-tag> activity) was measured using the <sd-tag id="sdTag47" source="sdapi" category="assay" entity_type="" role="" text="Proteasome Glo assay" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Proteasome Glo assay</sd-tag> where activity is proportional to the released <sd-tag id="sdTag48" source="sdapi" category="entity" entity_type="gene" role="reporter" text="luciferase" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">luciferase</sd-tag>. RFU, relative <sd-tag id="sdTag49" source="sdapi" category="entity" entity_type="gene" role="reporter" text="luciferase" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">luciferase</sd-tag> units. Data represent the mean ± SEM (n = 3, each experiment contained triplicates for each genotype). *p < 0.05.<graphic href="https://api.sourcedata.io/file.php?panel_id=14504"/></sd-panel></fig><fig id="4678"><title></title><label>Figure 2</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4678"/><sd-panel panel_id="14505">(A) Levels of soluble and insoluble <sd-tag id="sdTag55" source="sdapi" category="entity" entity_type="protein" role="assayed" text="α-synuclein" ext_ids="O55042" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Snca" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">α-synuclein</sd-tag> from <sd-tag id="sdTag58" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> of P1 <sd-tag id="sdTag59" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag60" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag56" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag>. <sd-tag id="sdTag57" source="sdapi" category="entity" entity_type="molecule" role="component" text="TX-100" ext_ids="CHEBI:9750" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="Triton X-100" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">TX-100</sd-tag> soluble and insoluble (<sd-tag id="sdTag64" source="sdapi" category="entity" entity_type="molecule" role="component" text="SDS" ext_ids="CHEBI:8984" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="sodium dodecyl sulfate" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">SDS</sd-tag>/<sd-tag id="sdTag269" source="sdapi" category="entity" entity_type="molecule" role="component" text="Urea" ext_ids="CHEBI:16199" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="urea" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Urea</sd-tag>) factions were isolated and analyzed via <sd-tag id="sdTag61" source="sdapi" category="assay" entity_type="" role="" text="western blotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">western blotting</sd-tag> with <sd-tag id="sdTag62" source="sdapi" category="entity" entity_type="protein" role="assayed" text="α-synuclein" ext_ids="O55042" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Snca" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">α-synuclein</sd-tag> antibodies. <sd-tag id="sdTag63" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="β-actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">β-actin</sd-tag> was used as a loading control.<graphic href="https://api.sourcedata.io/file.php?panel_id=14505"/></sd-panel><sd-panel panel_id="14506">(B) Sagittal <sd-tag id="sdTag66" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain stem" ext_ids="UBERON:0002298" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brainstem" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain stem</sd-tag> sections from <sd-tag id="sdTag67" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag68" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag69" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag70" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> were stained with <sd-tag id="sdTag71" source="sdapi" category="entity" entity_type="protein" role="assayed" text="α-synuclein" ext_ids="O55042" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Snca" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">α-synuclein</sd-tag> antibodies. Scale bar, 1,000 μm.<graphic href="https://api.sourcedata.io/file.php?panel_id=14506"/></sd-panel></fig><fig id="4679"><title></title><label>Figure 3</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4679"/><sd-panel panel_id="14507">(A) <sd-tag id="sdTag77" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> and <sd-tag id="sdTag73" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> from <sd-tag id="sdTag78" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag79" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag80" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag81" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> were stained with <sd-tag id="sdTag74" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag>. The mean florescence intensity in <sd-tag id="sdTag75" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="mitochondria" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondria</sd-tag> was analyzed via <sd-tag id="sdTag76" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag> (n = 3, >32 cells analyzed/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14507"/></sd-panel><sd-panel panel_id="14508">(B) <sd-tag id="sdTag91" source="sdapi" category="entity" entity_type="cell_type" role="component" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> from <sd-tag id="sdTag92" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag93" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− bathed in <sd-tag id="sdTag94" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> containing recording solution and fluorescence intensity analyzed via <sd-tag id="sdTag95" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. After 1 min, 1 μM <sd-tag id="sdTag82" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="oligomycin" ext_ids="CHEBI:25675" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="oligomycin" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">oligomycin</sd-tag> was added followed by 1 μM <sd-tag id="sdTag83" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> (n = 5, three cells analyzed/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14508"/></sd-panel><sd-panel panel_id="14509">(C) <sd-tag id="sdTag97" source="sdapi" category="entity" entity_type="cell_type" role="component" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> from <sd-tag id="sdTag98" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag99" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− incubated with 5 mM <sd-tag id="sdTag96" source="sdapi" category="entity" entity_type="molecule" role="component" text="methyl pyruvate" ext_ids="CHEBI:51850" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="methyl pyruvate" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">methyl pyruvate</sd-tag> 5 min prior to imaging. Cells bathed in 25 nM <sd-tag id="sdTag100" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> and 5 mM <sd-tag id="sdTag101" source="sdapi" category="entity" entity_type="molecule" role="component" text="methyl pyruvate" ext_ids="CHEBI:51850" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="methyl pyruvate" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">methyl pyruvate</sd-tag> containing recording solution and fluorescence intensity analyzed via <sd-tag id="sdTag102" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. After 90 s, 1 μM <sd-tag id="sdTag103" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="oligomycin" ext_ids="CHEBI:25675" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="oligomycin" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">oligomycin</sd-tag> was added, followed by 1 μM <sd-tag id="sdTag104" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> (n = 3, three cells analyzed/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14509"/></sd-panel><sd-panel panel_id="14510">(D) As in (C), except cells were bathed in 10 mM <sd-tag id="sdTag108" source="sdapi" category="entity" entity_type="molecule" role="component" text="methyl succinate" ext_ids="CHEBI:75146" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="monomethyl succinate" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">methyl succinate</sd-tag>, (n = 3, four cells/experiment). All data in this figure represent the mean ± SEM, *p < 0.05. <sd-tag id="sdTag109" source="sdapi" category="entity" entity_type="cell_type" role="component" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> from <sd-tag id="sdTag110" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag111" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− incubated with 5 mM methyl pyruvate 5 min prior to imaging. Cells bathed in 25 nM <sd-tag id="sdTag113" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> and 5 mM methyl pyruvate containing recording solution and fluorescence intensity analyzed via <sd-tag id="sdTag115" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. After 90 s, 1 μM <sd-tag id="sdTag116" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="oligomycin" ext_ids="CHEBI:25675" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="oligomycin" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">oligomycin</sd-tag> was added, followed by 1 μM <sd-tag id="sdTag117" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> (n = 3, three cells analyzed/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14510"/></sd-panel></fig><fig id="4680"><title></title><label>Figure 4</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4680"/><sd-panel panel_id="14511">(A) <sd-tag id="sdTag129" source="sdapi" category="assay" entity_type="" role="" text="Oxygen consumption rates" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Oxygen consumption rates</sd-tag> of <sd-tag id="sdTag123" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag124" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag125" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− mixed <sd-tag id="sdTag126" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> cultures. Basal <sd-tag id="sdTag121" source="sdapi" category="entity" entity_type="molecule" role="assayed" text="oxygen" ext_ids="CHEBI:25805" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="oxygen atom" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">oxygen</sd-tag> consumption was measured over 3 min. The maximal (uncoupled) rate was measured via the addition of <sd-tag id="sdTag127" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> and the non<sd-tag id="sdTag122" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="mitochondrial" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondrial</sd-tag> <sd-tag id="sdTag128" source="sdapi" category="entity" entity_type="molecule" role="assayed" text="oxygen" ext_ids="CHEBI:25805" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="oxygen atom" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">oxygen</sd-tag> consumption analyzed via the addition of <sd-tag id="sdTag130" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="antimycin A" ext_ids="CHEBI:22584" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="antimycin A" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">antimycin A</sd-tag> (n = 3, three runs/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14511"/></sd-panel><sd-panel panel_id="14512">(B) <sd-tag id="sdTag134" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="Complex I" ext_ids="GO:0005747" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrial respiratory chain complex I" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">Complex I</sd-tag>-<sd-tag id="sdTag140" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="NADH: Ubiquinone reductase" ext_ids="GO:0045257" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="succinate dehydrogenase complex (ubiquinone)" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">NADH: Ubiquinone reductase</sd-tag> activity from <sd-tag id="sdTag135" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag136" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag137" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag138" source="sdapi" category="entity" entity_type="tissue" role="component" text="brains" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brains</sd-tag> expressed as a ratio to <sd-tag id="sdTag133" source="sdapi" category="entity" entity_type="subcellular" role="normalizing" text="citrate synthase" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">citrate synthase</sd-tag> (n = 3).<graphic href="https://api.sourcedata.io/file.php?panel_id=14512"/></sd-panel><sd-panel panel_id="14513">(C) Complex II-III: <sd-tag id="sdTag143" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="Succinate dehydeogenase" ext_ids="GO:0045273" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="respiratory chain complex II" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">Succinate dehydeogenase</sd-tag>, <sd-tag id="sdTag144" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="cytochome c reductase" ext_ids="GO:0045275" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="respiratory chain complex III" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">cytochome c reductase</sd-tag> activity from <sd-tag id="sdTag145" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag146" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag147" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag148" source="sdapi" category="entity" entity_type="tissue" role="component" text="brains" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brains</sd-tag> expressed as a ratio to <sd-tag id="sdTag149" source="sdapi" category="entity" entity_type="subcellular" role="normalizing" text="citrate synthase" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">citrate synthase</sd-tag> (n = 3).<graphic href="https://api.sourcedata.io/file.php?panel_id=14513"/></sd-panel><sd-panel panel_id="14514">(D) <sd-tag id="sdTag152" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="Complex IV" ext_ids="GO:0005751" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrial respiratory chain complex IV" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">Complex IV</sd-tag> activity from <sd-tag id="sdTag153" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag154" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag155" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag156" source="sdapi" category="entity" entity_type="tissue" role="component" text="brains" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brains</sd-tag> expressed as a ratio to <sd-tag id="sdTag157" source="sdapi" category="entity" entity_type="subcellular" role="normalizing" text="citrate synthase" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">citrate synthase</sd-tag> (n = 3).<graphic href="https://api.sourcedata.io/file.php?panel_id=14514"/></sd-panel><sd-panel panel_id="14515">(E) <sd-tag id="sdTag168" source="sdapi" category="entity" entity_type="cell_type" role="component" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> were treated with 3 nM <sd-tag id="sdTag167" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="decylTPP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">decylTPP</sd-tag> and <sd-tag id="sdTag166" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="MitoQ10" ext_ids="11388331" norm_text="" ext_dbs="PubChem" in_caption="True" ext_names="Mitoquinone mesylate" ext_tax_ids="" ext_tax_names="" ext_urls="https://pubchem.ncbi.nlm.nih.gov/compound/">MitoQ10</sd-tag> for 48 hr and stained with <sd-tag id="sdTag169" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> and fluorescence intensity analyzed via <sd-tag id="sdTag170" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag> (n = 3, >16 cells/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14515"/></sd-panel><sd-panel panel_id="14516">(F) <sd-tag id="sdTag174" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+and <sd-tag id="sdTag175" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− cells treated with 3 nM <sd-tag id="sdTag176" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="decylTPP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">decylTPP</sd-tag> and <sd-tag id="sdTag173" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="MitoQ10" ext_ids="11388331" norm_text="" ext_dbs="PubChem" in_caption="True" ext_names="Mitoquinone mesylate" ext_tax_ids="" ext_tax_names="" ext_urls="https://pubchem.ncbi.nlm.nih.gov/compound/">MitoQ10</sd-tag> for 48 hr were subjected to <sd-tag id="sdTag177" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> using the indicted antibodies. All data in this figure represent the mean ± SEM, *p < 0.05.<graphic href="https://api.sourcedata.io/file.php?panel_id=14516"/></sd-panel></fig><fig id="4681"><title></title><label>Figure 5</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4681"/><sd-panel panel_id="14517">(A) <sd-tag id="sdTag187" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="Neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">Neurons</sd-tag> and <sd-tag id="sdTag188" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> were <sd-tag id="sdTag182" source="sdapi" category="assay" entity_type="" role="" text="immunostained" ext_ids="BAO_0002426" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunofluorescent labeling" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunostained</sd-tag> for <sd-tag id="sdTag183" source="sdapi" category="entity" entity_type="protein" role="assayed" text="cytochrome c" ext_ids="P62897" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Cycs" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">cytochrome c</sd-tag> and stained with <sd-tag id="sdTag184" source="sdapi" category="assay" entity_type="" role="" text="Hoechst" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Hoechst</sd-tag>. Far left panels were additionally <sd-tag id="sdTag189" source="sdapi" category="assay" entity_type="" role="" text="immunostained" ext_ids="BAO_0002426" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunofluorescent labeling" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunostained</sd-tag> for <sd-tag id="sdTag185" source="sdapi" category="entity" entity_type="protein" role="assayed" text="GFAP" ext_ids="P03995" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Gfap" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">GFAP</sd-tag> and <sd-tag id="sdTag186" source="sdapi" category="entity" entity_type="protein" role="assayed" text="MAP2" ext_ids="P20357" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Map2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">MAP2</sd-tag> to mark <sd-tag id="sdTag190" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag> and <sd-tag id="sdTag191" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag>. "A" in <sd-tag id="sdTag200" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="nucleus" ext_ids="GO:0005634" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="nucleus" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">nucleus</sd-tag> denotes <sd-tag id="sdTag192" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag>. Scale bar, 20 μm.(B) Mitochondrial morphology was blind counted from cells in (A) with <sd-tag id="sdTag193" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag> scored as <sd-tag id="sdTag194" source="sdapi" category="entity" entity_type="protein" role="assayed" text="MAP2" ext_ids="P20357" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Map2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">MAP2</sd-tag> positive and <sd-tag id="sdTag195" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> as <sd-tag id="sdTag196" source="sdapi" category="entity" entity_type="protein" role="assayed" text="GFAP" ext_ids="P03995" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Gfap" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">GFAP</sd-tag> positive. A "normal" morphology is classified as a mixture of fused and fragmented <sd-tag id="sdTag197" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="mitochondria" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondria</sd-tag> that comprise a wild-type network. (n = 3; 100 cells counted/experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14517"/></sd-panel><sd-panel panel_id="14518">(C) Levels of morphology proteins from <sd-tag id="sdTag201" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag202" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag203" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− isolated <sd-tag id="sdTag204" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mitochondria" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondria</sd-tag> were analyzed via <sd-tag id="sdTag205" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with the indicated antibodies.<graphic href="https://api.sourcedata.io/file.php?panel_id=14518"/></sd-panel><sd-panel panel_id="14519">(D) <sd-tag id="sdTag214" source="sdapi" category="entity" entity_type="tissue" role="component" text="Midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">Midbrain</sd-tag> <sd-tag id="sdTag215" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+, <sd-tag id="sdTag216" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/−, and <sd-tag id="sdTag217" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag218" source="sdapi" category="entity" entity_type="cell_type" role="component" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> expressing <sd-tag id="sdTag212" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag>-<sd-tag id="sdTag213" source="sdapi" category="entity" entity_type="gene" role="intervention" text="DRP1" ext_ids="74006" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Dnm1l" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">DRP1</sd-tag>K38A were <sd-tag id="sdTag219" source="sdapi" category="assay" entity_type="" role="" text="immunostained" ext_ids="BAO_0002426" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunofluorescent labeling" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunostained</sd-tag> for <sd-tag id="sdTag220" source="sdapi" category="entity" entity_type="protein" role="assayed" text="cytochrome c" ext_ids="P62897" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Cycs" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">cytochrome c</sd-tag> and <sd-tag id="sdTag221" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="mitochondrial" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondrial</sd-tag> morphologies analyzed; concurrently cells were stained with <sd-tag id="sdTag222" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> and fluorescence intensity analyzed via <sd-tag id="sdTag223" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. Scale bar, 20 μm (n = 3, >15 cells/experiment). All data in this figure represent the mean ± SEM.<graphic href="https://api.sourcedata.io/file.php?panel_id=14519"/></sd-panel></fig><fig id="4682"><title></title><label>Figure 6</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4682"/><sd-panel panel_id="14525">(A) <sd-tag id="sdTag226" source="sdapi" category="entity" entity_type="tissue" role="component" text="Midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">Midbrain</sd-tag> <sd-tag id="sdTag227" source="sdapi" category="entity" entity_type="cell_type" role="component" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> were transfected with <sd-tag id="sdTag228" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag>-<sd-tag id="sdTag233" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>, treated with 100 nM <sd-tag id="sdTag230" source="sdapi" category="entity" entity_type="molecule" role="component" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A1</sd-tag>, and stained with <sd-tag id="sdTag231" source="sdapi" category="assay" entity_type="" role="" text="MitoTracker Red" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">MitoTracker Red</sd-tag> and imaged using <sd-tag id="sdTag232" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>.<graphic href="https://api.sourcedata.io/file.php?panel_id=14525"/></sd-panel><sd-panel panel_id="14527">(B) <sd-tag id="sdTag237" source="sdapi" category="entity" entity_type="tissue" role="component" text="Midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">Midbrain</sd-tag> <sd-tag id="sdTag238" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag239" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag240" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag> and <sd-tag id="sdTag241" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="astrocytes" ext_ids="CL:0000127" norm_text="" ext_dbs="CL" in_caption="True" ext_names="astrocyte" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">astrocytes</sd-tag> were transfected with <sd-tag id="sdTag247" source="sdapi" category="entity" entity_type="protein" role="reporter" text="YFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">YFP</sd-tag>-<sd-tag id="sdTag248" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Parkin</sd-tag>. Half the transfected cells were treated for 1 hr with 10 μM <sd-tag id="sdTag242" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> and all bathed in <sd-tag id="sdTag243" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> containing recording solution and imaged using <sd-tag id="sdTag244" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. Scale bar, 20 μm.(C) <sd-tag id="sdTag245" source="sdapi" category="assay" entity_type="" role="" text="TMRM" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">TMRM</sd-tag> fluorescence intensity of cells from (B) was analyzed via <sd-tag id="sdTag246" source="sdapi" category="assay" entity_type="" role="" text="confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">confocal microscopy</sd-tag>. Data represent the mean ± SEM, (n = 3, >4 cells analyzed per experiment).<graphic href="https://api.sourcedata.io/file.php?panel_id=14527"/></sd-panel><sd-panel panel_id="14523">(D) <sd-tag id="sdTag252" source="sdapi" category="entity" entity_type="subcellular" role="component" text="Mitochondria" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">Mitochondria</sd-tag> within <sd-tag id="sdTag254" source="sdapi" category="entity" entity_type="tissue" role="component" text="midbrain" ext_ids="UBERON:0001891" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="midbrain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">midbrain</sd-tag> <sd-tag id="sdTag255" source="sdapi" category="entity" entity_type="cell_type" role="component" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag> were uncoupled by the addition of 10 μM <sd-tag id="sdTag256" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="FCCP" ext_ids="CHEBI:75458" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="carbonyl cyanide p-trifluoromethoxyphenylhydrazone" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">FCCP</sd-tag> for 1 and 6 hr. <sd-tag id="sdTag264" source="sdapi" category="entity" entity_type="protein" role="assayed" text="PINK1" ext_ids="Q99MQ3" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Pink1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">PINK1</sd-tag> expression analyzed via <sd-tag id="sdTag257" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> on isolated <sd-tag id="sdTag258" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mitochondria" ext_ids="GO:0005739" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="mitochondrion" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mitochondria</sd-tag> from <sd-tag id="sdTag259" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>+/+ and <sd-tag id="sdTag260" source="sdapi" category="entity" entity_type="gene" role="intervention" text="gba" ext_ids="14466" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Gba" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">gba</sd-tag>−/− <sd-tag id="sdTag261" source="sdapi" category="entity" entity_type="cell_type" role="component" text="neurons" ext_ids="CL:0000540" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">neurons</sd-tag>. Mitochondrial CI subunit <sd-tag id="sdTag265" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="NDUFS4" ext_ids="Q9CXZ1" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Ndufs4" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">NDUFS4</sd-tag> was used as a loading control.<graphic href="https://api.sourcedata.io/file.php?panel_id=14523"/></sd-panel></fig><fig id="4683"><title></title><label>Figure 7</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4683"/></fig></article>