F-type ATP synthase (F-ATPase) (F-ATPase)

F-type ATPases, also known as F-type ATP synthases or Complex V, are multi-subunit rotary enzymes found in the inner mitochondrial membranes of eukaryotes, the thylakoid membranes of plants, and the plasma membranes of bacteria [UniProt: P00846]. Their primary biological function is to synthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate, driven by a proton gradient across the membrane [StatPearls: NBK537027]. In certain conditions, they can also function in reverse, hydrolyzing ATP to pump protons. These enzymes play a critical role in cellular energy metabolism and are implicated in various pathological states, including mitochondrial disorders, cancer, and neurodegenerative diseases [PubMed: 28803868]. In the context of pharmacology, the mycobacterial F-type ATPase is a validated target for treating multi-drug-resistant tuberculosis, with the drug bedaquiline specifically inhibiting the enzyme's rotary mechanism [PubChem: CID 5388906]. Selectivity for bacterial over human mitochondrial ATP synthase is a key consideration in drug development to minimize host toxicity and potential cardiotoxic effects [PubMed: 32665454].

Other names

ATP synthaseF1F0-ATPaseComplex VMitochondrial ATP synthaseH+-transporting ATP synthase

Inhibition of the rotary mechanism of the F0 or F1 subunits, thereby blocking proton translocation and the subsequent synthesis of ATP [PMID: 24336209].