New gene on the block: Atg32--a specific receptor for selective mitophagy in S. cerevisiae.

摘要

Mitochondrial biogenesis and removal are under constant flux in growing cells but the mechanisms controlling the equilibrium between formation and degradation are not well understood. Cell dysfunction and disease have been attributed to defects in both processes but molecular genetic proof that defects in mitophagy-the specific removal of mitochondria by (macro) autophagy-cause disease processes is sparse. Mitochondria are clearly removed selectively under some conditions, and their removal may be blocked under disease conditions, so the existence of a specific mitochondrial tag that marks mitochondria for elimination by autophagy has long been postulated. There is recent evidence for proteins (e.g., Parkin, Nix) that serve as a mitochondrial address for mitophagy in mammalian cells but the mechanisms of coupling to the autophagic machinery are not yet clear. In yeast, Uthl and Aupl have been implicated in mitophagy, though how they operate, and whether macroautophagy is the mechanism of elimination, is not resolved. In a recent partial screen of Atg genes in yeast, mitophagy could be segregated from nonselective autophagy and the Cvt pathway, thus suggesting that a search for genes that control mitophagy specifically would be fruitful. Indeed, in a recent issue of Developmental Cell, two groups have independently provided compelling evidence for the existence of a specific, mitochondrial-resident tag for mitophagy in Saccharomyces cerevisiae, designated Atg32.9'10 Overviews (Puncta) by the two groups appear in this issue of Autophagy.