The paradox of mitochondrial dysfunction and extended longevity.
Mitochondria play numerous, essential roles in the life of eukaryotes. Disruption of mitochondrial function in humans is often pathological or even lethal. Surprisingly, in some organisms mitochondrial dysfunction can result in life extension. This paradox has been studied most extensively in the long-lived Mit mutants of the nematode Caenorhabditis elegans. In this review, we explore the major responses that are activated following mitochondrial dysfunction in these animals and how these responses potentially act to extend their life. We focus our attention on five broad areas of current research--reactive oxygen species signaling, the mitochondrial unfolded protein response, autophagy, metabolic adaptation, and the roles played by various transcription factors. Lastly, we also examine why disruption of complexes I and II differ in their ability to induce the Mit phenotype and extend lifespan.
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA; Department of Cell and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
Erin
E
Munkácsy
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA. Electronic address: reas3@uthscsa.edu.
Shane L
SL
Rea
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005838:Genotype; D006801:Humans; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response
D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors
Aging; C. elegans; Lifespan; Metabolism; Mit mutant; Mitochondria