NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans
NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans
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DOI：
10.7554/elife.19493
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发表时间：
2017-01-13
期刊：
影响因子：
7.7
通讯作者：
Hynes, Nancy E.
中科院分区：
文献类型：
--
作者：
Ewald, Collin Yves;Hourihan, John M.;Hynes, Nancy E.
线粒体来源的活性氧（ROS）的短暂增加激活适应性应激反应以促进寿命。烟酰胺腺嘌呤二核苷酸磷酸（Nicotinamide adenine dinucleotide phosphate， NADPH）氧化酶在响应各种刺激时产生局部活性氧，从而调节许多细胞过程，但其在衰老中的作用尚不清楚。在这里，我们发现秀丽隐杆线虫与erbb2驱动细胞运动的哺乳动物介质MEMO-1同源，是一种抑制BLI-3/NADPH氧化酶的蛋白质。MEMO-1与RHO-1/RhoA/GTPase络合，MEMO-1的缺失导致RHO-1与BLI-3/NADPH氧化酶的相互作用增强，从而刺激ROS的产生，ROS通过p38 MAP激酶向转录因子SKN-1/NRF1、2,3发出信号，从而促进抗逆性和长寿。无论是丢失memo-1还是通过过表达增加BLI-3/NADPH氧化酶活性都足以延长寿命。总之，这些发现表明，NADPH氧化酶诱导的氧化还原信号启动转录反应，保护细胞和生物体，并可以促进抗逆性和长寿。
Transient increases in mitochondrially-derived reactive oxygen species (ROS) activate an adaptive stress response to promote longevity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases produce ROS locally in response to various stimuli, and thereby regulate many cellular processes, but their role in aging remains unexplored. Here, we identified the C. elegans orthologue of mammalian mediator of ErbB2-driven cell motility, MEMO-1, as a protein that inhibits BLI-3/NADPH oxidase. MEMO-1 is complexed with RHO-1/RhoA/GTPase and loss of memo-1 results in an enhanced interaction of RHO-1 with BLI-3/NADPH oxidase, thereby stimulating ROS production that signal via p38 MAP kinase to the transcription factor SKN-1/NRF1,2,3 to promote stress resistance and longevity. Either loss of memo-1 or increasing BLI-3/NADPH oxidase activity by overexpression is sufficient to increase lifespan. Together, these findings demonstrate that NADPH oxidase-induced redox signaling initiates a transcriptional response that protects the cell and organism, and can promote both stress resistance and longevity.