Novel interactions between mitochondrial superoxide dismutases and the electron transport chain

Aging Cell

Wichit Suthammarak¹  Benjamin H. Somerlot²  Elyce Opheim¹  Margaret Sedensky¹ 

[1] Department of Anesthesiology and Pain Medicine, Center for Developmental Therapeutics, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA;Department of Genetics, Case Western Reserve University, Cleveland, OH, USA

关键词: lifespan;    superoxide dismutase;    reactive oxygen species;    electron transport chain;    supercomplexes;    heat shock protein;   

DOI  :  10.1111/acel.12144

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 the Anatomical Society and John Wiley & Sons Ltd