Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress.
Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress.
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DOI：
10.1016/j.celrep.2017.06.082
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发表时间：
2017-07-25
期刊：
影响因子：
8.8
通讯作者：
Kim JK
中科院分区：
文献类型：
--
作者：
Jin M;Fuller GG;Han T;Yao Y;Alessi AF;Freeberg MA;Roach NP;Moresco JJ;Karnovsky A;Baba M;Yates JR 3rd;Gitler AD;Inoki K;Klionsky DJ;Kim JK
糖酵解在低氧和高能量需求等条件下被上调，以促进细胞增殖，尽管其机制仍不清楚。我们发现，在酿酒酵母中的低氧诱导糖酵解酶的浓度，包括限速磷酸果糖激酶的Pfk2p亚单位，进入一个单一的，无膜结合的颗粒，称为“糖酵解体”或“G体”。酵母组筛选确定AMP激活的蛋白激酶Snf1p的酵母同源基因是G小体形成所必需的。蛋白质组学鉴定的许多G身体成分是G身体完整性所必需的。在低氧条件下不能形成G小体的细胞表现为细胞分裂异常，并产生不能存活的子细胞。相反，具有G小体的细胞表现出葡萄糖消耗增加和糖酵解中间产物水平降低。重要的是，人肝癌细胞在低氧条件下会形成G小体。综上所述，我们的结果表明，G小体的形成是一种保守的适应性反应，在缺氧或肿瘤发生期间增加糖酵解输出。金等人研究发现，低氧导致糖酵解酶在酿酒酵母和人肝癌细胞中被称为G小体的病灶中聚集。G小体形成是一种保守的兼性反应，可能有助于细胞在低氧条件下生存和增殖。
Glycolysis is upregulated under conditions such as hypoxia and high energy demand to promote cell proliferation, although the mechanism remains poorly understood. We find that hypoxia in Saccharomyces cerevisiae induces concentration of glycolytic enzymes, including the Pfk2p subunit of the rate-limiting phosphofructokinase, into a single, non-membrane-bound granule termed the “glycolytic body” or “G body”. A yeast kinome screen identifies the yeast ortholog of AMP-activated protein kinase, Snf1p, as necessary for G body formation. Many G body components identified by proteomics are required for G body integrity. Cells incapable of forming G bodies in hypoxia display abnormal cell division and produce inviable daughter cells. Conversely, cells with G bodies show increased glucose consumption and decreased levels of glycolytic intermediates. Importantly, G bodies form in human hepatocarcinoma cells in hypoxia. Together, our results suggest that G body formation is a conserved, adaptive response to increase glycolytic output during hypoxia or tumorigenesis. Jin et al. find that hypoxia leads to concentration of glycolytic enzymes into foci referred to as ‘G bodies’ in S. cerevisiae and human hepatocarcinoma cells. G body formation is a conserved, facultative response that may help cells survive and proliferate under low oxygen conditions.
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影响因子：
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DOI：
10.1073/pnas.1504822112
发表时间：
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影响因子：
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作者：
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通讯作者：
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