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ATP synthase peripheral stalk subunit OSCP, mitochondrial (ATP5PO)

Target
ATP5PO
Molecular classification
Enzyme (component of F-type ATPase/Complex V), Mitochondrial protein, Peripheral stalk subunit of ATP synthase
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Overview

ATP synthase peripheral stalk subunit OSCP, mitochondrial (ATP5PO), is a crucial structural and regulatory protein subunit of the mitochondrial ATP synthase complex (F1FO, Complex V). OSCP acts as a stator within the peripheral stalk, mechanically linking the catalytic F1 core to the membrane-embedded FO channel and maintaining complex integrity and coupling during rotary catalysis. The protein regulates sensitivity of the enzyme to oligomycin and modulates the opening of the mitochondrial permeability transition pore, interacting with agents such as cyclophilin D and Bz-423. Downregulation or dysfunction of OSCP is associated with mitochondrial disease, neurodegeneration (notably Alzheimer's disease), and cellular energy failure. The protein is encoded by the ATP5PO gene located on the long arm of chromosome 21.

Other names
ATP synthase peripheral stalk subunit OSCPATP5POATP5OATPOOSCPATP synthase subunit OOligomycin sensitivity conferral proteinOligomycin sensitivity conferring protein
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Mechanism of action

Inhibition of ATP synthase (by drugs such as oligomycin, effects conferred structurally by OSCP, but without direct ligand binding). Modulation of mitochondrial permeability transition pore (PTP) opening via interactions with cyclophilin D and Bz-423 at OSCP. Regulated by post-translational modifications such as acetylation and protonation of specific residues.

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Biological functions

ATP synthesis (proton motive force-driven ATP synthesis in mitochondria)Proton transmembrane transportConnector and structural support (mechanical linkage between catalytic core and membrane channel)Regulator of mitochondrial permeability transition pore (PTP)
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Disease associations

Mitochondrial Complex V deficiencyNeurodegenerative disease (notably, Alzheimer's disease)Potential links to cancer and metabolic dysregulation (by analogy with mitochondrial dysfunction in these diseases)
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Safety considerations

Targeting mitochondrial ATP synthase risks broad toxicity due to fundamental role in cellular energy metabolismInhibition may induce cell death, potentially damaging non-target tissues
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Interacting drugs

Oligomycin (complex inhibits ATP synthase activity, though oligomycin binds FO rather than OSCP)

1 more in the full profile.

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Biomarkers

Decreased expression of OSCP in neurodegeneration (e.g., Alzheimer's disease)OSCP downregulation associated with mitochondrial dysfunction and oxidative stress markers in disease models

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