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Mol Biol Cell. 2018 Jun 27:mbcE17120743. doi: 10.1091/mbc.E17-12-0743. [Epub ahead of print]

Lipid trafficking by yeast Snx4 family SNX-BAR proteins promotes autophagy and vacuole membrane fusion.

Author information

1
Department of Biology/Chemistry University of Osnabrück 49076 Osnabrück, Germany.
2
Department of Biology University of Utah Salt Lake City, UT 84112.
3
Department of Biological Sciences University of North Carolina at Charlotte Charlotte, North Carolina 28223.
4
Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06520.

Abstract

Cargo-selective and non-selective autophagy pathways employ a common core autophagy machinery that directs biogenesis of an autophagosome which eventually fuses with the lysosome to mediate turnover of macromolecules. In yeast ( Saccharomyces cerevisiae) cells, several selective autophagy pathways fail in cells lacking the dimeric Snx4/Atg24 and Atg20/Snx42 sorting nexins containing a BAR domain (SNX-BARs), which function as coat proteins of endosome-derived retrograde transport carriers. It is unclear if endosomal sorting by Snx4 proteins contributes to autophagy. Cells lacking Snx4 display a deficiency in starvation induced, non-selective autophagy that is severely exacerbated by ablation of mitochondrial phosphatidylethanolamine synthesis. Under these conditions, phosphatidylserine accumulates in the membranes of the endosome and vacuole, autophagy intermediates accumulate within the cytoplasm, and homotypic vacuole fusion is impaired. The Snx4-Atg20 dimer displays preference for binding and remodeling of phosphatidylserine-containing membrane in vitro, suggesting that Snx4-Atg20 coated carriers export phosphatidylserine-rich membrane from the endosome. Autophagy and vacuole fusion are restored by increasing phosphatidylethanolamine biosynthesis via alternative pathways, indicating that retrograde sorting by the Snx4 family sorting nexins maintains glycerophospholipid homeostasis required for autophagy and fusion competence of the vacuole membrane.

PMID:
29949447
DOI:
10.1091/mbc.E17-12-0743

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