NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. 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 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. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000128430Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
eLifeBand
Seiten / Artikelnummer
Verlag
eLife Sciences PublicationsOrganisationseinheit
09598 - Ewald, Collin Y. (ehemalig) / Ewald, Collin Y. (former)
Förderung
163898 - The role of extracellular matrix enhancement in promoting healthy aging (SNF)