NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans

eLife

Monet S Bland¹  John M Hourihan²  Iskra Katic³  T Keith Blackwell³  Joy Alcedo⁴  Carolin Obieglo⁴  Nancy E Hynes⁵  Lorenza E Moronetti Mazzeo⁵  Collin Yvès Ewald⁶ 

[1] Department of Genetics, Harvard Medical School, Boston, United States;Friedrich Miescher Institute for Biomedical Research, University of Basel, Basel, Switzerland;Harvard Stem Cell Institute, Cambridge, United States;Joslin Diabetes Center, Boston, United States;Department of Genetics, Harvard Medical School, Boston, United States;Department of Health Sciences and Technology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland;

关键词: NADPH oxidase;    longevity;    stress resistance;    reactive oxygen species;    SKN-1;    RHO-1;   

DOI  :  10.7554/eLife.19493

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown