Biosynthesis and regulation of the yeast vacuolar H⁺-ATPase

The yeast V-ATPase is highly similar to V-ATPase of higher organisms and has proved to be a biochemically and genetically accessible model for many aspects of V-ATPase function. Like other V-ATPase, the yeast enzyme consists of a complex of peripheral membrane proteins, the V₁ sector, attached to a complex of integral membrane subunits, the V₀ sector. Multiple pathways for biosynthetic assembly of the enzyme appear to be available to cells containing a full complement of subunits and enzyme activity may be further controlled during biosynthesis by a protease activity localized to the late Golgi apparatus. Surprisingly, the assembled V-ATPase is not a static structure. Instead, fully assembled V₁V₀ complexes appear to exist in a dynamic equilibrium with inactive cytosolic V₁ and membrane-bound V₀ complexes and this equilibrium can be rapidly shifted in response to changes in carbon source. The reversible disassembly of the yeast V-ATPase may be a novel regulatory mechanism, common to V-ATPase, that works in vivo in coordination with many other regulatory mechanisms.