title: C. elegans miro-1 Mutation Reduces the Amount of Mitochondria and Extends Life Span.
abstract: Mitochondria play a critical role in aging, however, the underlying mechanism is not well understood. We found that a mutation disrupting the C. elegans homolog of Miro GTPase (miro-1) extends life span. This phenotype requires simultaneous loss of miro-1 from multiple tissues including muscles and neurons, and is dependent on daf-16/FOXO. Notably, the amount of mitochondria in the miro-1 mutant is reduced to approximately 50% of the wild-type. Despite this reduction, oxygen consumption is only weakly reduced, suggesting that mitochondria of miro-1 mutants are more active than wild-type mitochondria. The ROS damage is slightly reduced and the mitochondrial unfolded protein response pathway is weakly activated in miro-1 mutants. Unlike previously described long-lived mitochondrial electron transport chain mutants, miro-1 mutants have normal growth rate. These results suggest that the reduction in the amount of mitochondria can affect the life span of an organism through activation of stress pathways.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Science Division, Yale-NUS College, Singapore, Singapore.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Natarie Pei Wen
authors.initials: NP
authors.lastname: Low
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hagen
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Science Division, Yale-NUS College, Singapore, Singapore.
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D010101:Oxygen Consumption; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species