Mitochondrial ATP synthase (Complex V) (Complex V)

Mitochondrial ATP synthase, also known as Complex V, is a multi-subunit enzyme complex located in the inner mitochondrial membrane that catalyzes the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate [UniProt: P06576]. This process is driven by the electrochemical proton gradient generated by the electron transport chain during oxidative phosphorylation [StatPearls: NBK493174]. The enzyme consists of two functional domains: the membrane-bound Fo domain, which acts as a proton channel, and the catalytic F1 domain, which protrudes into the mitochondrial matrix [PubMed: 29056340]. Beyond its primary role in energy production, ATP synthase is crucial for maintaining mitochondrial cristae structure and regulating the mitochondrial permeability transition pore (mPTP), which is involved in cell death pathways [PubMed: 28213343]. Mutations in subunits of this complex are linked to severe mitochondrial disorders such as Leigh syndrome and Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) [NIH: Genetic Home Reference]. In oncology, certain cancer cells exhibit a dependency on mitochondrial ATP production, making the complex a target for small molecules like "Gboxin" [PubMed: 29512651]. However, therapeutic targeting is challenging due to the risk of systemic toxicity and metabolic acidosis resulting from the inhibition of essential cellular respiration [PubMed: 30241614].

Other names

F1Fo-ATP synthaseATP synthase complexH+-transporting ATP synthaseMitochondrial ATPaseComplex V of the electron transport chainMitochondrial ATP production

Inhibition of the Fo subunit blocks the proton channel, while inhibition of the F1 subunit prevents the catalytic conversion of ADP to ATP; some modulators affect the rotary mechanism or the coupling efficiency between the proton motive force and ATP synthesis [PubMed: 29056340, PubMed: 16314577].