Mitochondrial F1FO ATP synthase complex (Complex V)

The mitochondrial F1FO ATP synthase complex, also known as Complex V, is a multi-subunit enzyme located in the inner mitochondrial membrane that plays a critical role in cellular energy production [StatPearls: NBK557482]. 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 [UniProt: P06576]. The complex consists of two functional domains: the F1 catalytic domain, which protrudes into the mitochondrial matrix, and the FO membrane-embedded domain, which facilitates proton translocation [PubMed: 30104378]. Beyond its primary role in bioenergetics, the ATP synthase is involved in the formation of the mitochondrial permeability transition pore (mPTP), influencing cell death pathways such as apoptosis and necrosis [PubMed: 29123138]. Dysregulation of this complex is linked to various pathologies, including mitochondrial DNA disorders like Leigh syndrome and NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa), as well as cancer, where metabolic reprogramming occurs [PubMed: 25659444]. Pharmacological targeting of the ATP synthase is explored in oncology to induce metabolic stress in cancer cells and in the treatment of infectious diseases, although selectivity remains a significant challenge due to its essential role in normal physiology [PubMed: 29512651].

Other names

F1F0-ATP synthaseMitochondrial ATP synthaseH+-transporting ATPaseATP synthase complexFoF1-ATPaseATP synthase, H+ transporting, mitochondrial F1 complex

Inhibition of the FO subunit to block proton translocation or inhibition of the F1 subunit to prevent ATP synthesis and hydrolysis [PubMed: 30104378].