ATP synthase (mitochondrial F1F0 complex) (ATP synthase (Complex V))

ATP synthase (Complex V) is a multi-subunit rotary enzyme embedded in the inner mitochondrial membrane where it catalyzes the synthesis of ATP from ADP and inorganic phosphate, powered by the proton-motive force generated by the respiratory chain complexes. Structurally, it consists of the F1 catalytic domain protruding into the mitochondrial matrix and the membrane-embedded Fo domain, functioning together through a rotary mechanism to convert electrochemical energy into chemical energy. Inhibitors of ATP synthase are under investigation for multiple therapeutic areas, particularly cancer (to target the metabolic vulnerabilities of malignant cells), neurodegenerative diseases (due to ATP synthase dysfunction or modification in disease pathogenesis), and infectious diseases. ATP synthase activity and modification are disease-biomarkers, and one or more subunits may be specifically targeted or dysregulated in various conditions[1][3][4][5][6][8].

Other names

F1F0-ATPaseComplex Vmitochondrial ATP synthaseH+-ATPase

Inhibition of proton translocation or rotary catalysis, blocking ATP synthesis; Non-competitive inhibition of F1-ATPase activity; Promotion of mitochondrial reactive oxygen species (ROS) (as a result of ATP synthase inhibition); Modulation of downstream energy-dependent cell signaling (e.g., AMPK/mTOR via J147).