title: NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity throughmemo-1inC. elegans.
abstract: 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 theC. elegansorthologue 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 ofmemo-1results 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 ofmemo-1or 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.
authors.affiliation: Department of Health Sciences and Technology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.|Friedrich Miescher Institute for Biomedical Research, University of Basel, Basel, Switzerland.|Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: Collin Yvès
authors.identifier: 0000-0003-1166-4171
authors.initials: CY
authors.lastname: Ewald
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Hourihan
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: Monet S
authors.initials: MS
authors.lastname: Bland
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: Carolin
authors.initials: C
authors.lastname: Obieglo
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, University of Basel, Basel, Switzerland.
authors.forename: Iskra
authors.initials: I
authors.lastname: Katic
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: Lorenza E
authors.initials: LE
authors.lastname: Moronetti Mazzeo
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, University of Basel, Basel, Switzerland.|Department of Biological Sciences, Wayne State University, Detroit, United States.
authors.forename: Joy
authors.initials: J
authors.lastname: Alcedo
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Joslin Diabetes Center, Boston, United States.|Harvard Stem Cell Institute, Cambridge, United States.
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, University of Basel, Basel, Switzerland.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hynes
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008136:Longevity; D019159:Nonheme Iron Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D019159:Nonheme Iron Proteins; C000626172:memo-1 protein, C elegans; C544706:Bli-3 protein, C elegans; D010088:Oxidoreductases
keywords: C. elegans; NADPH oxidase; RHO-1; SKN-1; cancer biology; cell biology; longevity; reactive oxygen species; stress resistance