ATP synthase membrane subunit g (mitochondrial) (ATP5MG)

Mitochondrial ATP synthase subunit g, encoded by the ATP5MG gene (formerly ATP5L), is a vital component of the F0 domain of the F1F0-ATP synthase complex (Complex V) (UniProt: O75964). Located in the inner mitochondrial membrane, this subunit plays a crucial role in the final step of oxidative phosphorylation by facilitating the translocation of protons across the membrane to drive ATP synthesis (GeneCards: ATP5MG). Beyond its role in energy production, subunit g is essential for the structural integrity of the peripheral stalk and the dimerization of ATP synthase complexes, which is necessary for the formation of mitochondrial cristae (PNAS, 2023). Dysregulation of ATP5MG is linked to various conditions, including mitochondrial diseases, metabolic syndrome-associated cardiovascular diseases, and neurodegenerative disorders like Alzheimer's disease (Frontiers in Cardiovascular Medicine, 2022). While not the primary target of most clinical drugs, it is directly inhibited by oligomycin and has been identified as a potential site of action for biguanides like metformin and certain nonsteroidal anti-inflammatory drugs (NSAIDs) (eLife, 2024; Google Patents: US20240000000). Therapeutic modulation of this target offers a pathway for treating metabolic and oncological diseases, though it carries risks of mitochondrial dysfunction, oxidative stress, and systemic metabolic disruption (MitoTox).

Other names

ATP5LATP5JGATPase subunit gMitochondrial ATP synthase subunit gATP synthase F(0) complex subunit gATP synthase G chain, mitochondrial

Inhibition of the F0 proton channel; modulation of the peripheral stalk assembly; regulation of mitochondrial membrane potential and cristae organization.