Autophagy induction under carbon starvation conditions is negatively regulated by carbon catabolite repression
Autophagy induction under carbon starvation conditions is negatively regulated by carbon catabolite repression
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DOI：
10.1074/jbc.m117.817510
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发表时间：
2017-12-01
影响因子：
4.8
通讯作者：
Ohsumi, Yoshinori
中科院分区：
文献类型：
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作者：
Adachi, Atsuhiro;Koizumi, Michiko;Ohsumi, Yoshinori
自噬是一个保守的过程，其中细胞质组分被隔离以在真核细胞的液泡/溶酶体中降解。自噬在各种饥饿条件下诱导，例如氮、碳、磷、锌等的耗尽。然而，除了氮饥饿，目前还不清楚这些刺激如何诱导自噬。例如，在酵母中，在碳饥饿条件下是否诱导自噬仍然存在争议，各种报道都表明在碳耗尽时诱导和缺乏诱导。因此，我们进行了一项分析，以解释这些不一致之处，得出的结论是，当细胞以甘油而不是葡萄糖作为碳源生长时，自噬是响应于突然的碳饥饿而诱导的。我们发现，在这些条件下，自噬是介导的非选择性降解，这是高度依赖于自噬体相关的支架蛋白Atg11和Atg17。我们还发现，碳饥饿诱导的自噬程度与细胞的耗氧速率呈正相关，从而将自噬诱导与呼吸代谢联系起来。进一步的生化分析表明，细胞内ATP水平的维持也是碳饥饿诱导的自噬所必需的，并且自噬在长期碳饥饿期间的细胞活力中起着重要作用。我们的研究结果表明，碳饥饿诱导的自噬是负调控的碳分解代谢物阻遏。
Autophagy is a conserved process in which cytoplasmic components are sequestered for degradation in the vacuole/lysosomes in eukaryotic cells. Autophagy is induced under a variety of starvation conditions, such as the depletion of nitrogen, carbon, phosphorus, zinc, and others. However, apart from nitrogen starvation, it remains unclear how these stimuli induce autophagy. In yeast, for example, it remains contentious whether autophagy is induced under carbon starvation conditions, with reports variously suggesting both induction and lack of induction upon depletion of carbon. We therefore undertook an analysis to account for these inconsistencies, concluding that autophagy is induced in response to abrupt carbon starvation when cells are grown with glycerol but not glucose as the carbon source. We found that autophagy under these conditions is mediated by nonselective degradation that is highly dependent on the autophagosome-associated scaffold proteins Atg11 and Atg17. We also found that the extent of carbon starvation-induced autophagy is positively correlated with cells' oxygen consumption rate, drawing a link between autophagy induction and respiratory metabolism. Further biochemical analyses indicated that maintenance of intracellular ATP levels is also required for carbon starvation-induced autophagy and that autophagy plays an important role in cell viability during prolonged carbon starvation. Our findings suggest that carbon starvation-induced autophagy is negatively regulated by carbon catabolite repression.