Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae

XieM.; RoyR.

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Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae

机译：过氧化氢水平的增加会导致AMPK线虫幼虫的脂质代谢受到HIF-1依赖性修饰

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Cells have evolved numerous mechanisms to circumvent stresses caused by the environment, and many of them are regulated by the AMP-activated kinase (AMPK). Unlike most organisms, C. elegans AMPK-null mutants are viable, but they die prematurely in the "long-lived" dauer stage due to exhaustion of triglyceride stores. Using a genome-wide RNAi approach, we demonstrate that the disruption of genes that increase hydrogen peroxide levels enhance the survival of AMPK mutant dauers by altering both the abundance and the nature of the fatty-acid content in the animal by increasing the HIF-1-dependent expression of several key enzymes involved in fatty-acid biosynthesis. Our data provide a mechanistic foundation to explain how an optimal level of an often vilified ROS-generating compound such as hydrogen peroxide can provide cellular benefit, a phenomenon described as hormesis, by instructing cells to readjust their lipid biosynthetic capacity through downstream HIF-1 activation to correct cellular energy deficiencies.

机译：细胞已经进化出许多机制来规避由环境引起的压力，并且它们中的许多受到AMP激活激酶（AMPK）的调节。与大多数生物不同，秀丽隐杆线虫AMPK-null突变体是可行的，但由于甘油三酸酯存储的耗尽，它们在“长寿” dauer阶段过早死亡。使用全基因组的RNAi方法，我们证明了通过增加HIF-1来改变动物体内脂肪酸含量的丰度和性质，从而破坏增加过氧化氢水平的基因，从而提高AMPK突变体dauers的存活率。脂肪酸生物合成中几种关键酶的依赖表达。我们的数据提供了一个机械基础，可以解释最佳水平的经常被破坏的产生ROS的化合物（如过氧化氢）如何通过指示细胞通过下游HIF-1激活来重新调节其脂质生物合成能力，从而提供细胞益处（一种被描述为兴奋现象）。纠正细胞能量不足。

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《Cell metabolism》 |2012年第3期|共14页
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XieM.; RoyR.;
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中图分类内分泌腺疾病及代谢病;
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1. Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae [J] . XieM., RoyR. Cell metabolism . 2012,第3期

机译：过氧化氢水平的增加会导致AMPK线虫幼虫的脂质代谢受到HIF-1依赖性修饰
2. Neuroendocrine regulation of fat metabolism by autophagy gene atg‐18 in C.?elegans dauer larvae [J] . Ray Jia, Jiuli Zhang, Kailiang Jia FEBS Open Bio . 2019,第9期

机译：秀丽隐杆线虫幼虫自噬基因atg-18对脂肪代谢的神经内分泌调控
3. Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling. [J] . Narbonne P, Roy R Development . 2006,第4期

机译：在秀丽隐杆线虫发育过程中抑制种系增殖需要PTEN，LKB1和AMPK信号传导。
4. Molecular Genetics and Quantitative Proteomics to Identify Novel Regulatory Mechanisms of Lipid and Energy Metabolism in C. elegans [C] . Julius Fredens, Kasper Engholm-Keller, Jakob Moller-Jensen, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2012

机译：分子遗传学和定量蛋白质组学，以鉴定C.秀丽隐杆线虫脂质和能量代谢的新调节机制
5. Neuroendocrine regulation of fat metabolism by autophagy gene atg‐18 in C. elegans dauer larvae [O] . Ray Jia, Jiuli Zhang, Kailiang Jia -1

机译：线虫幼虫自噬基因atg-18对脂肪代谢的神经内分泌调节
6. Increased Levels of Hydrogen Peroxide Induce a HIF-1-dependent Modification of Lipid Metabolism in AMPK Compromised C. elegans Dauer Larvae [O] . Xie Meng, Roy Richard 2012

机译：过氧化氢水平升高导致AMPK线虫Dauer幼虫脂质代谢的HIF-1依赖性修饰

Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae

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