ATPase-ATP Synthase and Mitochondrial Pathology

Abstract

ATP, the main energy source of biological systems is mainly synthesized during oxidative phosphorylations: electron transfer along the respiratory chain located in the mitochondrial inner membrane is coupled to ATP synthesis from ADP and inorganic phosphate. The enzyme responsible for this synthesis is the ATPase-ATP synthase, FO-Fl or complex V (EC 3.6.1.34), identified in 1960 by Racker et al. To explain the coupling between electron transfer and ATP synthesis, Mitchell proposed the chemiosmotic theory in 1961, according to which an electrochemical proton gradient, established during electron transfer across the inner mitochondrial membrane represents the proton-motive force used by FO-Fl to synthesize ATP (review, Mitchell 1979). Over the last 20 years, the F0-Fl structure has been partly resolved by sequencing its subunits or their genes and by analysis of the 3-D structure of Fl (Abrahams et al. 1994; review, Pedersen et al. 1994, 1996). Many biochemical studies made on the native enzyme, or after chemical or genetic modification of the enzyme, have served as a basis to elucidate the mechanisms explaining how proton transfer across F0 could induce conformational changes inside Fl that would induce ATP synthesis (reviews, Boyer 1997; Junge et al. 1997). The final understanding of the molecular mechanism of this coupling will probably await the resolution of the F0 structure.

Due to space limitation, the authors apologize for not being able to cite all the articles where the original work was described. More often than not, the references are limited to reviews where the reader can find the original citations