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

Cargo-selective and nonselective autophagy pathways employ a common core autophagy machinery that directs biogenesis of an autophagosome that eventually fuses with the lysosome to mediate turnover of macromolecules. In yeast ( Saccharomyces cerevisiae) cells, several selective autophagy pathways fai...

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Published in:Molecular biology of the cell 2018-09, Vol.29 (18), p.2190-2200
Main Authors: Ma, Mengxiao, Kumar, Santosh, Purushothaman, Latha, Babst, Markus, Ungermann, Christian, Chi, Richard J, Burd, Christopher G
Format: Article
Language:English
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Summary:Cargo-selective and nonselective autophagy pathways employ a common core autophagy machinery that directs biogenesis of an autophagosome that 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 whether endosomal sorting by Snx4 proteins contributes to autophagy. Cells lacking Snx4 display a deficiency in starvation induced, nonselective 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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e17-12-0743