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Structure, function and regulation of the vacuolar (H + )‐ATPases
Author(s) -
Forgac Michael
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01425-2
Subject(s) - v atpase , atpase , f atpase , atp hydrolysis , cytosol , biochemistry , chemistry , microbiology and biotechnology , proton transport , intracellular , biophysics , biology , enzyme , membrane , thylakoid , chloroplast , gene
The vacuolar (H + )‐ATPases (or V‐ATPases) function to acidify intracellular compartments in eukaryotic cells, playing an important role in such processes as receptor‐mediated endocytosis, intracellular membrane traffic, protein degradation and coupled transport. V‐ATPases in the plasma membrane of specialized cells also function in renal acidification, bone resorption and cytosolic pH maintenance. The V‐ATPases are composed of two domains. The V 1 domain is a 570‐kDa peripheral complex composed of 8 subunits (subunits A–H) of molecular weight 70–13 kDa which is responsible for ATP hydrolysis. The V 0 domain is a 260‐kDa integral complex composed of 5 subunits (subunits a–d) which is responsible for proton translocation. The V‐ATPases are structurally related to the F‐ATPases which function in ATP synthesis. Biochemical and mutational studies have begun to reveal the function of individual subunits and residues in V‐ATPase activity. A central question in this field is the mechanism of regulation of vacuolar acidification in vivo. Evidence has been obtained suggesting a number of possible mechanisms of regulating V‐ATPase activity, including reversible dissociation of V 1 and V 0 domains, disulfide bond formation at the catalytic site and differential targeting of V‐ATPases. Control of anion conductance may also function to regulate vacuolar pH. Because of the diversity of functions of V‐ATPases, cells most likely employ multiple mechanisms for controlling their activity.