snz/SNX25 at the crossroad of endocytosis and lipid handling in autophagy

Abstract

Macroautophagy/autophagy is coupled to a myriad of intracellular processes, among which vesicular trafficking is an important contributor of membranes and proteins required at various stages, from autophagosome formation to degradation. Hence, understanding how membrane trafficking is coupled to autophagy induction and how cells rewire trafficking upon high autophagic needs is instrumental to our understanding of autophagy. In our recent manuscript, we tested a known class of endosomal sorting regulators, the sorting nexin family, for their involvement in autophagy in Drosophila. We identified snz (snazarus) as an important regulator of autophagy in Drosophila as well as in mammalian cells, by demonstrating a role for the snz human ortholog SNX25 in HeLa cells. Using knockout rescue experiments, we observed that SNX25 loss affects many cellular processes, namely VAMP8 endocytosis and lipid handling. Mutational studies identified separate protein domains involved in these processes. Given the role of this sorting nexin family in lipid droplet regulation, our work expands their requirement to autophagy.

Keywords

• autophagy
• lipid metabolism
• snazarus
• sorting nexin 25
• vamp8