Effects of the mitochondrial respiratory chain on longevity in C. elegans.
How an organism ages is a question that has fascinated biologists, and the elderly, for centuries. One useful approach to understanding complex processes such as aging is to study genetic variation in model organisms such as the nematode, Caenorhabditis elegans. Classical mutant strains and RNAi screens have demonstrated that mitochondrial function is a major factor affecting longevity. Recent advances in the biochemical methods for studying mitochondrial functions have extended the usefulness of C. elegans for deciphering the molecular mechanisms by which mitochondria determine lifespan. Defects of all complexes in the mitochondrial respiratory chain have been described and have varied effects on lifespan. The phenotypes of these mutants indicate that the locality, production rate, and/or steady-state level of reactive oxygen species (ROS) is a defining lifespan-determining factor in these mutants. Mutants of enzymes involved in ROS scavenging have also been described, such as mitochondrial superoxide dismutases, and reveal a complex connection between ROS and lifespan. Energy balance, transcriptional signaling pathways, stress tolerance, and metabolic restructuring are also tied to ROS, and may also play roles in the mutants' altered lifespans. In this review, we discuss how findings with C. elegans genetics extend our understanding of the contributions of the mitochondrial respiratory chain and ROS to the process of aging.
Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 Ninth Avenue C9S-9, Seattle, WA 98199, USA. Electronic address: Beverley.m.dancy@gmail.com.
Beverley M
BM
Dancy
Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 Ninth Avenue C9S-9, Seattle, WA 98199, USA. Electronic address: Margaret.sedensky@seattlechildrens.org.
Margaret M
MM
Sedensky
Center for Developmental Therapeutics, Seattle Children's Research Institute, 1900 Ninth Avenue C9S-9, Seattle, WA 98199, USA. Electronic address: Philip.morgan@seattlechildrens.org.
Philip G
PG
Morgan
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D005838:Genotype; D008136:Longevity / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D010641:Phenotype
D029742:Caenorhabditis elegans Proteins; D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins
Aging; Caenorhabditis elegans; Genetics; Lifespan; Mitochondrial respiratory chain; Reactive oxygen species