NADPH Oxidase-Mediated Redox Signaling Promotes Oxidative Stress Resistance and Longevity Through memo-1 in C. elegans

Elife. 2017 Jan 13;6:e19493. doi: 10.7554/eLife.19493.

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.

Keywords: C. elegans; NADPH oxidase; RHO-1; SKN-1; cancer biology; cell biology; longevity; reactive oxygen species; stress resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / metabolism*
  • Longevity*
  • Nonheme Iron Proteins / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Oxidoreductases / antagonists & inhibitors*
  • Signal Transduction*

Substances

  • Caenorhabditis elegans Proteins
  • Nonheme Iron Proteins
  • memo-1 protein, C elegans
  • Bli-3 protein, C elegans
  • Oxidoreductases