ATP synthase peripheral stalk subunit OSCP, mitochondrial

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.