RRC ID 30654
Author Yee C, Yang W, Hekimi S.
Title The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans.
Journal Cell
Abstract The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by an elevation of mtROS does not affect apoptosis but protects from the consequences of mitochondrial dysfunction by triggering a unique pattern of gene expression that modulates stress sensitivity and promotes survival. In vertebrates, mtROS induce apoptosis through the intrinsic pathway to protect from severely damaged cells. Our observations in nematodes demonstrate that sensing of mtROS by the apoptotic pathway can, independently of apoptosis, elicit protective mechanisms that keep the organism alive under stressful conditions. This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging.
Volume 157(4)
Pages 897-909
Published 2014-5-8
DOI 10.1016/j.cell.2014.02.055
PII S0092-8674(14)00359-6
PMID 24813612
PMC PMC4454526
MeSH Adenosine Triphosphate / metabolism Aging Animals Apoptosis* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Electron Transport / genetics Electron Transport Complex III / genetics Electron Transport Complex III / metabolism Longevity* Mitochondria / metabolism* Oxygen / metabolism Reactive Oxygen Species / metabolism* Signal Transduction Superoxide Dismutase / metabolism Transcriptome
IF 31.398
Times Cited 102
C.elegans tm783 tm760