RRC ID 45850
Author Schaar CE, Dues DJ, Spielbauer KK, Machiela E, Cooper JF, Senchuk M, Hekimi S, Van Raamsdonk JM.
Title Mitochondrial and cytoplasmic ROS have opposing effects on lifespan.
Journal PLoS Genet.
Abstract Reactive oxygen species (ROS) are highly reactive, oxygen-containing molecules that can cause molecular damage within the cell. While the accumulation of ROS-mediated damage is widely believed to be one of the main causes of aging, ROS also act in signaling pathways. Recent work has demonstrated that increasing levels of superoxide, one form of ROS, through treatment with paraquat, results in increased lifespan. Interestingly, treatment with paraquat robustly increases the already long lifespan of the clk-1 mitochondrial mutant, but not other long-lived mitochondrial mutants such as isp-1 or nuo-6. To genetically dissect the subcellular compartment in which elevated ROS act to increase lifespan, we deleted individual superoxide dismutase (sod) genes in clk-1 mutants, which are sensitized to ROS. We find that only deletion of the primary mitochondrial sod gene, sod-2 results in increased lifespan in clk-1 worms. In contrast, deletion of either of the two cytoplasmic sod genes, sod-1 or sod-5, significantly decreases the lifespan of clk-1 worms. Further, we show that increasing mitochondrial superoxide levels through deletion of sod-2 or treatment with paraquat can still increase lifespan in clk-1;sod-1 double mutants, which live shorter than clk-1 worms. The fact that mitochondrial superoxide can increase lifespan in worms with a detrimental level of cytoplasmic superoxide demonstrates that ROS have a compartment specific effect on lifespan - elevated ROS in the mitochondria acts to increase lifespan, while elevated ROS in the cytoplasm decreases lifespan. This work also suggests that both ROS-dependent and ROS-independent mechanisms contribute to the longevity of clk-1 worms.
Volume 11(2)
Pages e1004972
Published 2015-2
DOI 10.1371/journal.pgen.1004972
PII PGENETICS-D-14-02541
PMID 25671321
PMC PMC4335496
MeSH Aging / genetics* Aging / pathology Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Electron Transport / genetics Electron Transport Complex III / genetics Longevity / genetics* Mitochondria / genetics* Mitochondria / metabolism Oxidative Stress* Reactive Oxygen Species / metabolism* Signal Transduction Superoxide Dismutase / genetics Superoxides / metabolism
IF 5.54
Times Cited 31
WOS Category GENETICS & HEREDITY
Resource
C.elegans tm776 tm783 tm760 tm1146 tm1246