A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans.
When mitochondrial respiration or ubiquinone production is inhibited in Caenorhabditis elegans, behavioral rates are slowed and lifespan is extended. Here, we show that these perturbations increase the expression of cell-protective and metabolic genes and the abundance of mitochondrial DNA. This response is similar to the response triggered by inhibiting respiration in yeast and mammalian cells, termed the "retrograde response". As in yeast, genes switched on in C. elegans mitochondrial mutants extend lifespan, suggesting an underlying evolutionary conservation of mechanism. Inhibition of fstr-1, a potential signaling gene that is up-regulated in clk-1 (ubiquinone-defective) mutants, and its close homolog fstr-2 prevents the expression of many retrograde-response genes and accelerates clk-1 behavioral and aging rates. Thus, clk-1 mutants live in "slow motion" because of a fstr-1/2-dependent pathway that responds to ubiquinone. Loss of fstr-1/2 does not suppress the phenotypes of all long-lived mitochondrial mutants. Thus, although different mitochondrial perturbations activate similar transcriptional and physiological responses, they do so in different ways.
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
David
D
Cristina
Michael
M
Cary
Adam
A
Lunceford
Catherine
C
Clarke
Cynthia
C
Kenyon
D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration; D005786:Gene Expression Regulation; D008136:Longevity; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D009154:Mutation
D029742:Caenorhabditis elegans Proteins