2017/01/13 by Collin Y. Ewald, John M Hourihan, Monet S. Bland +6 · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Neuroscience · #Genetics, Aging, and Longevity in Model Organisms #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Neuroinflammation and Neurodegeneration Mechanisms
paper · doi:10.7554/elife.19493
openalex publication_date 2017/01/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.