ATP synthase inhibitory factor subunit 1 (ATP5IF1)

ATP synthase inhibitory factor subunit 1 (ATP5IF1) is a mitochondrial protein that acts as a specific endogenous inhibitor of the mitochondrial ATP synthase (F1Fo-ATPase, complex V). It binds to and inhibits ATP synthase activity when the mitochondrial membrane potential collapses, such as during hypoxia or ischemia, preventing the enzyme from switching to ATP hydrolysis that would deplete cellular ATP stores[2][3]. ATP5IF1 plays a critical regulatory role in energy metabolism, promoting a metabolic shift from oxidative phosphorylation to glycolysis (Warburg effect), influencing cell fate, and protecting cells during mitochondrial stress. It is implicated in cancer, metabolic diseases, myopathies, and serves as a biomarker for some pathologies[1][3]. Under normal conditions, its activity is regulated by pH-dependent oligomerization and phosphorylation, as well as interaction with transcription factors involved in metabolic reprogramming such as c-Myc and PGC1α[1][2]. No approved therapeutic drugs specifically target ATP5IF1, but it is under investigation as a possible target for modulating cancer metabolism and other mitochondrial disorders[1].

Other names

ATPase inhibitor, mitochondrialATPase inhibitory factor 1IF1IF(1)ATPIF1ATPIIPATPIPATP5IF1pMGC1167MGC8898Endogenous F(1)F(o)-ATPase inhibitorInhibitor of F(1)F(o)-ATPaseATP synthase inhibitor proteinATPase inhibitor proteinATP synthase F1 subunit epsilonhATP5IF1

Inhibition of ATP synthase (complex V) under low mitochondrial membrane potential or stress, preventing wasteful ATP hydrolysis. Metabolic reprogramming (e.g., promoting glycolysis, inhibiting oxidative phosphorylation).