Golgi membrane-associated degradation pathway in yeast and mammals
Golgi membrane-associated degradation pathway in yeast and mammals
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DOI：
10.15252/embj.201593191
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发表时间：
2016-09-15
期刊：
影响因子：
11.4
通讯作者：
Shimizu, Shigeomi
中科院分区：
文献类型：
--
作者：
Yamaguchi, Hirofumi;Arakawa, Satoko;Shimizu, Shigeomi
自噬是降解亚细胞成分的细胞过程，并且从酵母到哺乳动物都是保守的。虽然自噬被认为是活细胞所必需的，但缺乏Atg5或Atg7的细胞是健康的，这表明存在非经典降解途径来补偿自噬的缺乏。在这项研究中，我们表明，芽殖酵母酿酒酵母，其中缺乏Atg5，进行大量的蛋白质降解使用高尔基介导的结构，以补偿自噬时，用阿替霉素B1，多烯抗真菌药物治疗。我们将此机制命名为高尔基体膜相关降解（GOMED）途径。这一过程是由破坏PI（4）P依赖的从高尔基体的顺行运输驱动的，它也存在于Atg5缺陷的哺乳动物细胞中。在生物学上，当在葡萄糖剥夺培养基中培养Atg5缺陷的β细胞系和Atg7缺陷的β细胞时，发生从高尔基体分泌胰岛素颗粒的破坏，并且诱导GOMED消化这些（原）胰岛素颗粒。总之，在自噬缺陷的酵母和哺乳动物细胞中，GOMED通过破坏PI（4）P依赖的顺行运输而被激活。
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 beta-cell line and Atg7-deficient beta-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.