ATP synthase (Complex V) (Complex V)

ATP synthase, also known as Complex V, is a multi-subunit enzyme complex located in the inner mitochondrial membrane that plays a critical role in cellular energy production (UniProt, 2023). It utilizes the electrochemical proton gradient generated by the electron transport chain to catalyze the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (StatPearls, 2023). Beyond its primary role in bioenergetics, the complex is involved in maintaining mitochondrial cristae structure and regulating the mitochondrial permeability transition pore, which is central to apoptosis (Wikipedia, 2024). Mutations in subunits of this complex are linked to various mitochondrial encephalomyopathies, such as Leigh syndrome and NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) (NIH, 2023). In pharmacology, ATP synthase is a validated target for antimicrobial therapy, exemplified by the drug bedaquiline used for multi-drug-resistant tuberculosis (PubMed, 2014). Additionally, researchers are investigating ATP synthase inhibitors as potential anti-cancer agents to exploit the unique metabolic dependencies of certain tumor cells (Nature, 2019).

Other names

F1Fo-ATP synthaseMitochondrial ATPaseMitochondrial complex VH+-transporting ATP synthaseATP synthase complex

Inhibition of the proton-translocating Fo domain or the catalytic F1 domain to prevent ATP synthesis or hydrolysis (PubMed, 2014; StatPearls, 2023).