RRC ID 47491
Author Yamaguchi H, Arakawa S, Kanaseki T, Miyatsuka T, Fujitani Y, Watada H, Tsujimoto Y, Shimizu S.
Title Golgi membrane-associated degradation pathway in yeast and mammals.
Journal EMBO J
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.
Volume 35(18)
Pages 1991-2007
Published 2016-9-15
DOI 10.15252/embj.201593191
PII embj.201593191
PMID 27511903
PMC PMC5282831
MeSH Amphotericin B / metabolism Animals Antifungal Agents / metabolism Autophagy-Related Protein 5 / deficiency Cells, Cultured Golgi Apparatus / metabolism* Insulin-Secreting Cells / metabolism Intracellular Membranes / metabolism* Metabolic Networks and Pathways* Mice, Inbred C57BL Proinsulin / metabolism Proteolysis* Saccharomyces cerevisiae / drug effects Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / metabolism* Saccharomyces cerevisiae Proteins
IF 9.889
Times Cited 29
DNA material pHYA1122 (RDB14521) pHYA1123 (RDB14522) pHYA1126 (RDB14523) pHYA1127 (RDB14524) pHYA1133 (RDB14525) pHYA1165 (RDB14526) pHYA1166 (RDB14527) pHYA1530 (RDB14528).