title: Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice.
abstract: Mitochondrial function is an important determinant of the ageing process; however, the mitochondrial properties that enable longevity are not well understood. Here we show that optimal assembly of mitochondrial complex I predicts longevity in mice. Using an unbiased high-coverage high-confidence approach, we demonstrate that electron transport chain proteins, especially the matrix arm subunits of complex I, are decreased in young long-living mice, which is associated with improved complex I assembly, higher complex I-linked state 3 oxygen consumption rates and decreased superoxide production, whereas the opposite is seen in old mice. Disruption of complex I assembly reduces oxidative metabolism with concomitant increase in mitochondrial superoxide production. This is rescued by knockdown of the mitochondrial chaperone, prohibitin. Disrupted complex I assembly causes premature senescence in primary cells. We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Satomi
authors.initials: S
authors.lastname: Miwa
authors.affiliation: Centre for Integrated Systems Biology of Ageing and Nutrition, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Howsun
authors.initials: H
authors.lastname: Jow
authors.affiliation: Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Baty
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Rafal
authors.initials: R
authors.lastname: Czapiewski
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Saretzki
authors.affiliation: Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: Achim
authors.initials: A
authors.lastname: Treumann
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
mesh_terms: D000375:Aging; D019588:Aging, Premature; D000818:Animals; D002460:Cell Line; D042967:Electron Transport Complex I / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000091402:Prohibitins; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics
chemical_list: D000091402:Prohibitins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C118906:NDUFB9 protein, human; C472512:NDUFS3 protein, human