Human mitochondrial F-ATP synthase (Complex V)

Human mitochondrial F-ATP synthase, also known as Complex V, is a sophisticated multi-subunit enzyme complex located within the inner mitochondrial membrane. Its primary biological function is the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate, a process powered by the proton motive force generated by the electron transport chain during oxidative phosphorylation (Walker, 2013). In addition to energy production, the complex plays a structural role in shaping mitochondrial cristae and is a key regulator of the mitochondrial permeability transition pore (mPTP), which influences cell death and survival (Jonckheere et al., 2012). Mutations in the nuclear or mitochondrial genes encoding its subunits lead to severe metabolic disorders, including Leigh syndrome and NARP (neuropathy, ataxia, and retinitis pigmentosa). In oncology, the enzyme is often upregulated or modified to support the metabolic demands of cancer cells, making it a potential target for small-molecule inhibitors like Gboxin (Chung et al., 2021). However, therapeutic intervention is challenging due to the risk of systemic toxicity, as ATP synthase is essential for the function of almost all aerobic cells.

Other names

Complex VF1F0-ATP synthaseMitochondrial ATPaseATP5H+-transporting two-sector ATPaseMitochondrial F-type ATPase

Direct inhibition of the F1 catalytic sector or the F0 proton-conducting sector, leading to the cessation of ATP synthesis and dissipation of the mitochondrial membrane potential.