ATP synthase (F1F0-ATP synthase) (ATP5)

ATP synthase, traditionally localized to the inner mitochondrial membrane, is also found on the plasma membrane of several cell types, most notably endothelial cells, where it is termed ectopic or cell surface ATP synthase [Moser et al., 1999, PNAS; Chi and Pizzo, 2006, Drug Discov Today]. On the endothelial cell surface, it functions as a receptor for angiostatin, an endogenous inhibitor of angiogenesis, and plays a pivotal role in regulating extracellular ATP levels and local pH [Moser et al., 1999, PNAS; Yamamoto et al., 2007, Cancer Sci]. This enzyme is involved in the proliferation, migration, and survival of endothelial cells, making it a key player in tumor-associated angiogenesis [Chi and Pizzo, 2006, Drug Discov Today; Chang et al., 2012, J Biomed Sci]. Drugs like angiostatin and certain small molecules, such as citreoviridin, bind to the F1 domain of the enzyme, inhibiting its catalytic activity and leading to endothelial cell apoptosis [Moser et al., 1999, PNAS; Huang et al., 2008, J Biol Chem]. Because its expression is significantly upregulated on the surface of tumor-activated endothelial cells compared to normal tissues, it represents a selective target for anti-angiogenic cancer therapies [Chi and Pizzo, 2006, Drug Discov Today; Pan et al., 2011, Cancer Res]. Targeting this enzyme offers a unique approach to disrupting the metabolic and signaling environment required for tumor growth and metastasis [Chang et al., 2012, J Biomed Sci].

Other names

Ecto-ATP synthaseCell surface ATP synthaseEctopic ATP synthaseF1F0-ATPaseAngiostatin receptor

Inhibition of the catalytic F1 domain of ATP synthase, which disrupts the regulation of extracellular ATP/ADP levels and local pH, leading to intracellular ATP depletion and induction of apoptosis in endothelial cells [Moser et al., 1999, PNAS; Chi and Pizzo, 2006, Drug Discov Today].