title: Novel interactions between mitochondrial superoxide dismutases and the electron transport chain.
abstract: The processes that control aging remain poorly understood. We have exploited mutants in the nematode, Caenorhabditis elegans, that compromise mitochondrial function and scavenging of reactive oxygen species (ROS) to understand their relation to lifespan. We discovered unanticipated roles and interactions of the mitochondrial superoxide dismutases (mtSODs): SOD-2 and SOD-3. Both SODs localize to mitochondrial supercomplex I:III:IV. Loss of SOD-2 specifically (i) decreases the activities of complexes I and II, complexes III and IV remain normal; (ii) increases the lifespan of animals with a complex I defect, but not the lifespan of animals with a complex II defect, and kills an animal with a complex III defect; (iii) induces a presumed pro-inflammatory response. Knockdown of a molecule that may be a pro-inflammatory mediator very markedly extends lifespan and health of certain mitochondrial mutants. The relationship between the electron transport chain, ROS, and lifespan is complex, and defects in mitochondrial function have specific interactions with ROS scavenging mechanisms. We conclude that mtSODs are embedded within the supercomplex I:III:IV and stabilize or locally protect it from reactive oxygen species (ROS) damage. The results call for a change in the usual paradigm for the interaction of electron transport chain function, ROS release, scavenging, and compensatory responses.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Wichit
authors.initials: W
authors.lastname: Suthammarak
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Somerlot
authors.forename: Elyce
authors.initials: E
authors.lastname: Opheim
authors.forename: Margaret
authors.initials: M
authors.lastname: Sedensky
authors.forename: Philip G
authors.initials: PG
authors.lastname: Morgan
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D019069:Cell Respiration; D004579:Electron Transport; D047108:Embryonic Development; D008136:Longevity; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction; D013482:Superoxide Dismutase / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C525107:Sod-3 protein, C elegans; C027576:4-hydroxy-2-nonenal
keywords: electron transport chain; heat shock protein; lifespan; reactive oxygen species; supercomplexes; superoxide dismutase
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