Function, structure, and biogenesis of mitochondrial ATP synthase

The energy needs of aerobic organisms are met principally through the action of ATP synthases (F1F0). These enzymes, found in the inner membrane of mitochondria, the thylakoid membrane of chloroplasts, and the plasma membrane of bacteria, catalyze the synthesis of ATP from ADP and Pi using the energy of an electrochemical transmembrane proton gradient (for review, see (1-3)). ATP synthases are multimeric proteins with a molecular mass of approximately 550,000 Daltons. Historically, their structure has been described in terms of two sectors that can be separated from one another under nondenaturing conditions: A hydrophobic domain (F0) that contains the proton channel and a hydrophilic ATPase (F1) containing the nucleotide binding and catalytic sites. Membrane-bound F1 catalyzes both ATP synthesis and ATP hydrolysis, coupled to the movement of protons through F0 from one side of the membrane to the other. When detached from the membrane, F1 catalyzes ATP hydrolysis but not ATP synthesis. The latter reaction requires the energy of the electrochemical proton gradient. This chapter briefly reviews some recent advances in the areas of the subunit structure and the different functions of the ATP synthase, but focuses mainly on the roles of mitochondrial and nuclear gene products in biogenesis of the mitochondrial enzyme. Most of the discussion related to biogenesis will be centered on the ATP synthase of Saccharomyces cerevisiae since it is studies of this particular enzyme that have provided much of the currently available information on this topic. As a facultative anaerobe, S. cerevisiae is well-suited for such studies because it can survive on fermentable carbon sources in the absence of mitochondrial respiration or oxidative phosphorylation. While all ATP synthases have similar gross structures and catalytic mechanism, the mitochondrial enzymes have acquired a set of subunit polypeptides during evolution that are absent in bacteria and chloroplasts. The subunit compositions of the mammalian and S. cerevisiae F1F0 are almost identical, underscoring the usefulness of yeast as a model for gaining information relevant to mitochondrial ATP synthases in higher eukaryotes. © 2005 Elsevier Inc. All rights reserved.