Mitochondrial proton-transporting 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 ATP from ADP and inorganic phosphate (Source: UniProt P06576). This process is driven by the electrochemical proton gradient generated by the electron transport chain during oxidative phosphorylation. In the context of oncology, many cancer cells—particularly cancer stem cells and those in hypoxic or nutrient-poor environments—rely on mitochondrial ATP synthase to maintain energy homeostasis and prevent apoptosis (Source: Song et al., Journal of Hematology & Oncology, 2021). Pharmacological inhibition of this machinery, using agents like Gboxin or repurposed drugs like bedaquiline, can selectively disrupt the metabolic adaptation of cancer cells, leading to mitochondrial dysfunction and cell death (Source: Shi et al., Nature, 2019; Fiorillo et al., Aging, 2016). However, because ATP synthase is essential for the function of high-energy organs like the heart and brain, developing inhibitors with a favorable therapeutic index remains a significant challenge in drug development (Source: Sennoune et al., Cancers, 2020).

Other names

F1Fo-ATP synthaseMitochondrial ATP synthaseATPaseATP5ATP synthase complex

Inhibition of the Fo or F1 subunits to block proton translocation and ATP catalytic activity, leading to metabolic crisis.