A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.
We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.
Lee
Siu Sylvia
SS
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Lee
Raymond Y N
RY
Fraser
Andrew G
AG
Kamath
Ravi S
RS
Ahringer
Julie
J
Ruvkun
Gary
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics*; D005820:Genetic Testing; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D034622:RNA Interference; D013312:Stress, Physiological / Q000378:metabolism
D000255:Adenosine Triphosphate; D007935:Leucine-tRNA Ligase