NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans.
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.
['Ewald|Collin Yvès|CY|0000-0003-1166-4171', 'Hourihan|John M|JM|', 'Bland|Monet S|MS|', 'Obieglo|Carolin|C|', 'Katic|Iskra|I|', 'Moronetti Mazzeo|Lorenza E|LE|', 'Alcedo|Joy|J|', 'Blackwell|T Keith|TK|', 'Hynes|Nancy E|NE|']
D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D008136:Longevity D019159:Nonheme Iron Proteins D010084:Oxidation-Reduction D018384:Oxidative Stress D010088:Oxidoreductases D015398:Signal Transduction
stress resistance longevity C. elegans reactive oxygen species NADPH oxidase RHO-1 SKN-1 cancer biology cell biology