Yeast and mammalian autophagosomes exhibit distinct phosphatidylinositol 3-phosphate asymmetries

Jinglei Cheng, Akikazu Fujita, Hayashi Yamamoto, Tsuyako Tatematsu, Soichiro Kakuta, Keisuke Obara, Yoshinori Ohsumi and Toyoshi Fujimoto ()
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Jinglei Cheng: Nagoya University Graduate School of Medicine
Akikazu Fujita: Nagoya University Graduate School of Medicine
Hayashi Yamamoto: Frontier Research Center, Tokyo Institute of Technology
Tsuyako Tatematsu: Nagoya University Graduate School of Medicine
Soichiro Kakuta: Frontier Research Center, Tokyo Institute of Technology
Keisuke Obara: Frontier Research Center, Tokyo Institute of Technology
Yoshinori Ohsumi: Frontier Research Center, Tokyo Institute of Technology
Toyoshi Fujimoto: Nagoya University Graduate School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Phosphatidylinositol 3-kinase is indispensable for autophagy but it is not well understood how its product, phosphatidylinositol 3-phosphate (PtdIns(3)P), participates in the biogenesis of autophagic membranes. Here, by using quick-freezing and freeze-fracture replica labelling, which enables determination of the nanoscale distributions of membrane lipids, we show that PtdIns(3)P in yeast autophagosomes is more abundant in the luminal leaflet (the leaflet facing the closed space between the outer and inner autophagosomal membranes) than in the cytoplasmic leaflet. This distribution is drastically different from that of the mammalian autophagosome in which PtdIns(3)P is confined to the cytoplasmic leaflet. In mutant yeast lacking two cytoplasmic phosphatases, ymr1Δ and sjl3Δ, PtdIns(3)P in the autophagosome is equally abundant in the two membrane leaflets, suggesting that the PtdIns(3)P asymmetry in wild-type yeast is generated by unilateral hydrolysis. The observed differences in PtdIns(3)P distribution suggest that autophagy in yeast and mammals may involve substantially different processes.

Date: 2014
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DOI: 10.1038/ncomms4207

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