title: Golgi membrane-associated degradation pathway in yeast and mammals.
abstract: Autophagy is a cellular process that degrades subcellular constituents, and is conserved from yeast to mammals. Although autophagy is believed to be essential for living cells, cells lacking Atg5 or Atg7 are healthy, suggesting that a non-canonical degradation pathway exists to compensate for the lack of autophagy. In this study, we show that the budding yeast Saccharomyces cerevisiae, which lacks Atg5, undergoes bulk protein degradation using Golgi-mediated structures to compensate for autophagy when treated with amphotericin B1, a polyene antifungal drug. We named this mechanism Golgi membrane-associated degradation (GOMED) pathway. This process is driven by the disruption of PI(4)P-dependent anterograde trafficking from the Golgi, and it also exists in Atg5-deficient mammalian cells. Biologically, when an Atg5-deficient β-cell line and Atg7-deficient β-cells were cultured in glucose-deprived medium, a disruption in the secretion of insulin granules from the Golgi occurred, and GOMED was induced to digest these (pro)insulin granules. In conclusion, GOMED is activated by the disruption of PI(4)P-dependent anterograde trafficking in autophagy-deficient yeast and mammalian cells.
authors: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
authors: Hirofumi
authors: H
authors: Yamaguchi
authors: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
authors: Satoko
authors: S
authors: Arakawa
authors: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
authors: Toku
authors: T
authors: Kanaseki
authors: Department of Medicine, Metabolism & Endocrinology, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Miyatsuka
authors: Department of Medicine, Metabolism & Endocrinology, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors: Yoshio
authors: Y
authors: Fujitani
authors: Department of Medicine, Metabolism & Endocrinology, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors: Hirotaka
authors: H
authors: Watada
authors: Department of Molecular and Cellular Biology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Osaka, Japan.
authors: Yoshihide
authors: Y
authors: Tsujimoto
authors: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan shimizu.pcb@mri.tmd.ac.jp.
authors: Shigeomi
authors: 0000-0002-8437-0791
authors: S
authors: Shimizu
mesh_terms: D000666:Amphotericin B / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D000071187:Autophagy-Related Protein 5 / Q000172:deficiency; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008810:Mice, Inbred C57BL; D011384:Proinsulin / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: C102268:ATG5 protein, S cerevisiae; D000935:Antifungal Agents; D000071187:Autophagy-Related Protein 5; D029701:Saccharomyces cerevisiae Proteins; D000666:Amphotericin B; D011384:Proinsulin
keywords: GOMED; Golgi membrane; anterograde trafficking; autophagy