caa a22 4500 528785605 20190908091347.0 cr unu---uuuuu 180924e201701 xx s 000 0 eng 10.3929/ethz-b-000128430 doi 10.7554/eLife.19493 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/128430 NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. Elegans [Elektronische Daten] [Collin Ewald, id_orcid 0000-0003-1166-4171, John M. Hourihan, Monet S. Bland, Carolin Obieglo, Iskra Katic, Lorenza E.M. Mazzeo, Joy Alcedo, T. Keith Blackwell, Nancy E. Hynes] Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Ewald Collin joint author id_orcid 0000-0003-1166-4171 joint author Hourihan John M. joint author Bland Monet S. joint author Obieglo Carolin joint author Katic Iskra joint author Mazzeo Lorenza E.M. joint author Alcedo Joy joint author Blackwell T. Keith joint author Hynes Nancy E. joint author eLife Cambridge : eLife Sciences Publications 6, p. e19493 2050-084X http://hdl.handle.net/20.500.11850/128430 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/128430 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Ewald Collin joint author ETHRESEARCH 700 -- id_orcid 0000-0003-1166-4171 joint author ETHRESEARCH 700 1- Hourihan John M. joint author ETHRESEARCH 700 1- Bland Monet S. joint author ETHRESEARCH 700 1- Obieglo Carolin joint author ETHRESEARCH 700 1- Katic Iskra joint author ETHRESEARCH 700 1- Mazzeo Lorenza E.M. joint author ETHRESEARCH 700 1- Alcedo Joy joint author ETHRESEARCH 700 1- Blackwell T. Keith joint author ETHRESEARCH 700 1- Hynes Nancy E. joint author ETHRESEARCH 773 0- eLife Cambridge : eLife Sciences Publications 6, p. e19493 2050-084X BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access