• Open Access

Novel interactions between mitochondrial superoxide dismutases and the electron transport chain

Authors

  • Wichit Suthammarak,

    1. Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA
    Current affiliation:
    1. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Bangkok-noi, Bangkok, Thailand
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    • These authors contributed equally as primary authors to this article.
  • Benjamin H. Somerlot,

    1. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
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    • These authors contributed equally as primary authors to this article.
    • Deceased.
  • Elyce Opheim,

    1. Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA
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  • Margaret Sedensky,

    1. Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA
    2. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
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    • These authors contributed equally as senior authors to this article.
  • Philip G. Morgan

    Corresponding author
    1. Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA
    2. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
    • Correspondence

      Philip G Morgan, Seattle Children's Research Institute, 1900 9th Ave, Seattle, WA 98101, USA. Tel.: +1 206-884-1101; fax: +1 206-987-7661; e-mail: pgm4@uw.edu

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    • These authors contributed equally as senior authors to this article.

Summary

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.

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