Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.
Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.
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DOI：
10.1371/journal.pone.0145836
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Jacobs HT
中科院分区：
文献类型：
--
作者：
Kemppainen E;George J;Garipler G;Tuomela T;Kiviranta E;Soga T;Dunn CD;Jacobs HT
果蝇突变体tko 25t表现出线粒体蛋白质合成的缺陷，导致呼吸和氧化磷酸化的全面不足。这导致发育延迟和对机械应力诱导的癫痫发作敏感的生物表型。我们发现，突变表型加剧了剂量依赖性的方式由高饮食糖水平。发现tko 25t幼虫表现出严重的代谢异常，高糖饮食进一步加剧了这种异常。这些包括丙酮酸盐和乳酸盐升高，ATP和NADPH降低。饮食中补充丙酮酸或乳酸模拟了高糖的影响。基于组织特异性拯救，这种代谢危机开始的关键组织是肠道。它伴随着细胞溶质蛋白质合成和分泌的RNA和翻译后水平的下调，包括在蛋白质水平的S6激酶的新的调节。
The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level.