Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae |
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Authors: | Maki Yamagata Keisuke Obara Akio Kihara |
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Institution: | Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan |
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Abstract: | In eukaryotes, autophagy is a conserved protein degradation system that degrades cytoplasmic components by encompassing them with double-membrane structures, called autophagosomes, and delivering them to the lytic compartments of vacuoles/lysosomes. Certain Atg proteins are known to be involved in autophagy, yet the identity and function of lipid molecules involved remain largely unknown. We investigated the involvement of sphingolipids in autophagy using Saccharomyces cerevisiae. Inhibiting synthesis of the simplest complex sphingolipid, inositol phosphorylceramide (IPC), resulted in reduced autophagic activities. Similar results were obtained using myriocin, an inhibitor of the first step in sphingolipid synthesis. Our results indicate that sphingolipids, especially IPC, are required for autophagy. Inhibition of sphingolipid synthesis had no effect on formation of Atg12-Atg5 or Atg8-phosphatidylethanolamine conjugates, on maturation of vacuolar proteases, or on formation of the pre-autophagosomal structure (PAS). These results suggest that sphingolipids are not involved in the cellular signaling that leads to formation of the PAS, but may be involved in the process of autophagosome formation. |
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Keywords: | Abbreviations: AbA aureobasidin A ALP alkaline phosphatase ApeI aminopeptidase I Cer ceramide CPY carboxypeptidase Y Cvt cytoplasm to vacuole targeting DHS dihydrosphingosine IPC inositol phosphorylceramide MIPC mannosylinositol phosphorylceramide M(IP)2C mannosyldiinositol phosphorylceramide Myr myriocin PAS pre-autophagosomal structure PE phosphatidylethanolamine PHS phytosphingosine SC synthetic complete S(-NC) synthetic medium deprived nitrogen and carbon sources |
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