Structure and Function of F- and V-ATPases

F- and V-ATPases are amazing rotary machines that have the common feature of coupling ATP hydrolysis to H⁺ pumping. They share many structural and mechanistic features. V-ATPases are found in lysosomes and other cellular locations, such endosomes and secretory vesicles, where they play a key role in organellar acidification and therefore in protein processing through the secretory pathway or protein degradation during autophagy or phagocytosis. V-ATPases are also expressed at the plasma membrane of cells specialized in active proton secretion, such as osteoclasts and renal intercalated cells. V-ATPases have been implicated in several pathologies, including cancer, where they are involved in maintenance of the acidic microenvironment and in nutrient supply, making them attractive therapeutic targets. F-ATP synthases are found in prokaryotes as well as in the mitochondria and chloroplasts of eukaryotes, where they have evolved the ability to harness gradients of ions (most frequently H⁺) to synthesize ATP. Coupled to respiration-driven H⁺ extrusion, this is a key feature that allows energy conservation with high efficiency. In mitochondria, F-ATP synthase also plays a structural role, forming V-shaped dimers essential for a normal inner membrane cristae morphology. An intriguing feature of mitochondrial F-ATP synthases has also been proposed, i.e. the Ca²⁺ -dependent formation of energy-dissipating channels which may coincide with the permeability transition pore. Recent years have seen a rapid increase of our understanding of the structural and functional features of these enzyme complexes, as well as an expansion of their proposed roles in physiology and pathology. This Research Topic covers most aspects of F- and V-ATPases structure and function, and is meant to provide an updated view of both established facts and open questions in a rapidly moving field.