Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans.
Increased protection from reactive oxygen species (ROS) is believed to increase life span. However, it has not been clearly demonstrated that endogenous ROS production actually limits normal life span. We have identified a mutation in the Caenorhabditis elegans iron sulfur protein (isp-1) of mitochondrial complex III, which results in low oxygen consumption, decreased sensitivity to ROS, and increased life span. Furthermore, combining isp-1(qm150) with a mutation (daf-2) that increases resistance to ROS does not result in any significant further increase in adult life span. These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way.
Feng
J
J
Department of Biology, McGill University, 1205 Avenue Dr Penfield, H3A 1B1, Montréal, Québec, Canada.
Bussière
F
F
Hekimi
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics; D014450:Electron Transport Complex III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D010269:Paraquat / Q000494:pharmacology; D010641:Phenotype; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D003573:Cytochrome b Group; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins; D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C443102:Isp-1 protein, Caenorhabditis elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D014450:Electron Transport Complex III; D010269:Paraquat; D010100:Oxygen