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首页> 外文期刊>Current Biology: CB >Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity
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Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity

机译：抑制呼吸通过增加HIF-1活性的活性氧来延长秀丽隐杆线虫的寿命。

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摘要

A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice [1-10], but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia [11, 12]. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration [1, 4, 13]. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.
机译：轻度抑制线粒体呼吸可延长许多生物的寿命，包括酵母，蠕虫，果蝇和小鼠[1-10]，但其潜在机制尚不清楚。降低呼吸速率的一种环境条件是缺氧（低氧）。因此，有可能感觉到氧气的机制在减少呼吸的寿命响应中起作用。缺氧诱导因子HIF-1是高度保守的转录因子，可激活在缺氧期间促进存活的基因[11，12]。在这项研究中，我们表明抑制线虫的呼吸作用可以通过激活HIF-1来促进寿命。通过全基因组筛选，我们发现许多编码呼吸链成分的基因的RNA干扰（RNAi）敲低诱导了hif-1依赖性转录。此外，HIF-1对于延长clk-1和isp-1突变体的寿命是必需的，这些突变体降低了呼吸频率[1、4、13]。抑制呼吸似乎可以通过提高活性氧（ROS）的水平来激活HIF-1。我们发现，呼吸突变体中的ROS升高，而ROS的轻度升高可刺激HIF-1激活基因表达并延长寿命。这样，HIF-1似乎将线粒体中的呼吸压力与促进寿命的核转录反应联系起来。

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