Fungal mitochondrial ATP synthase (F-ATPase)

Fungal mitochondrial ATP synthase is a multi-subunit enzyme complex located in the inner mitochondrial membrane, responsible for the production of the majority of cellular adenosine triphosphate (ATP) through oxidative phosphorylation [1]. It consists of two main domains: the membrane-bound F0 sector, which facilitates proton translocation, and the peripheral F1 sector, which contains the catalytic sites for ATP synthesis [2]. This enzyme is essential for the growth, survival, and virulence of various pathogenic fungi, including species of Candida, Aspergillus, and Cryptococcus [3]. By coupling the flow of protons down their electrochemical gradient to the mechanical rotation of the enzyme's central stalk, it drives the synthesis of ATP from ADP and inorganic phosphate [4]. Because of its central role in fungal bioenergetics, it is considered a promising target for the development of new antifungal agents, particularly to combat drug-resistant strains [5]. However, the high structural homology between fungal and human ATP synthases necessitates the identification of fungal-specific binding sites to avoid host mitochondrial toxicity [6].

Other names

Mitochondrial F1F0-ATP synthaseComplex VMitochondrial ATPaseATP phosphohydrolase

Inhibition of the F0 proton channel or the F1 catalytic domain, preventing the synthesis of ATP and disrupting the mitochondrial membrane potential.