protein
ATP synthase peripheral stalk subunit OSCP, mitochondrial
Gene
ATP5PO
Organism
Homo sapiens(9606)
Length
213 aa
Mass
23,277 Da
ATP5PO (ATP synthase peripheral stalk subunit OSCP) is a 213-amino acid mitochondrial protein that forms part of the peripheral stalk of ATP synthase (Complex V). This component acts as a stator, anchoring the catalytic domain relative to the rotating central stalk during ATP synthesis from ADP coupled to the proton gradient generated by the electron transport chain (UniProt: P48047).
The protein localizes to the mitochondrial membrane as part of the F₀ domain and peripheral stalk of the ATP synthase complex. Pathogenic variants in ATP5PO cause mitochondrial complex V deficiency, nuclear type 7 (MC5DN7), a severe autosomal recessive disorder presenting with hypotonia, developmental delay, epileptic encephalopathy, and progressive neurodegeneration (UniProt: P48047).
In Alzheimer's disease, ATP5PO shows ambiguous directional changes across subcellular fractions from post-mortem AD brain tissue compared to age-matched controls, with a modest mean log2 fold-change of 0.34 (Chaparral AD proteomics). The inconsistent direction suggests differential regulation depending on cellular compartmentalization or disease stage, warranting further investigation into mitochondrial ATP synthase dysfunction in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
⚠ Ambiguous — detected in AD samples, direction unclear across fractionsP3
-0.377
P2
not detected
S2
+1.061
S3
not detected
Mean log₂FC across detected fractions: +0.3418 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Subunit OSCP, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). Part of the complex F(0) domain (PubMed:37244256). Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements (By similarity)
Disease associations
Mitochondrial complex V deficiency, nuclear type 7MC5DN7
An autosomal recessive, severe, mitochondrial disorder apparent soon after birth. It is characterized by multisystemic features that include hypotonia, developmental delay, progressive epileptic encephalopathy, progressive cerebral atrophy, white matter abnormalities on brain imaging, and hypertrophic cardiomyopathy in some patients. Death in infancy or early childhood may occur.
Sources
Last updated 5/8/2026, 6:27:05 AM