Essential and distinct roles of phosphatidylinositol 4-kinases,Pik1p and Stt4p,in yeast autophagy |
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| Institution: | 1. Department of Molecular and Cell Biology and Biochemistry, Basic Veterinary Science, Faculty of Veterinary Medicine, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan;2. Education and Research Center for Fermentation Studies, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan;3. Medical Research Institute, Tokyo Women''s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;1. Field of Veterinary Pathobiology, Basic Veterinary Science, Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan;2. Medical Research Institute, Tokyo Women''s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;1. Department of Biochemistry, University of Toronto, Toronto, ON, Canada;2. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada;3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada;4. Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada;5. Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland |
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| Abstract: | Autophagy is a degradative cellular pathway that protects eukaryotic cells from starvation/stress. Phosphatidylinositol 4-kinases, Pik1p and Stt4p, are indispensable for autophagy in budding yeast, but participation of PtdIns-4 kinases and their product, phosphatidylinositol 4-phosphate PtdIns(4)P], is not understood. Nanoscale membrane lipid distribution analysis showed PtdIns(4)P is more abundant in yeast autophagosomes in the luminal leaflet than the cytoplasmic leaflet. PtdIns(4)P is confined to the cytoplasmic leaflet of autophagosomal inner and outer membranes in mammalian cells. Using temperature-conditional single PIK1 or STT4 PtdIns 4-kinase mutants, autophagic bodies in the vacuole of PIK1 and STT4 mutant cells dramatically decreased at restrictive temperatures, and the number of autophagosomes in the cytosol of PIK1 mutants cells was also decreased, whereas autophagosome levels of STT4 mutant cells were comparable to that of wild-type and STT4 mutant cells at permissive temperatures. Localization of PtdIns(4)P in the luminal leaflet in the biological membrane is a novel finding, and differences in PtdIns(4)P distribution suggest substantial differences between yeast and mammals. We also demonstrate in this study that Pik1p and Stt4p play essential roles in autophagosome formation and autophagosome–vacuole fusion in yeast cells, respectively. |
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