RRC ID 46208
Author Suthammarak W, Somerlot BH, Opheim E, Sedensky M, Morgan PG.
Title Novel interactions between mitochondrial superoxide dismutases and the electron transport chain.
Journal Aging Cell
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.
Volume 12(6)
Pages 1132-40
Published 2013-12-1
DOI 10.1111/acel.12144
PMID 23895727
PMC PMC3838459
MeSH Aldehydes / metabolism Animals Antioxidants / metabolism Caenorhabditis elegans / embryology Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / metabolism* Cell Respiration Electron Transport Embryonic Development Longevity Mitochondria / enzymology* Mitochondrial Proteins / metabolism Multiprotein Complexes / metabolism Oxidative Phosphorylation Oxidative Stress Protein Binding RNA, Messenger / genetics RNA, Messenger / metabolism Reproduction Superoxide Dismutase / metabolism*
IF 7.238
Times Cited 33
C.elegans tm760