Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases

Exp Gerontol. 2006 Oct;41(10):974-91. doi: 10.1016/j.exger.2006.06.060. Epub 2006 Sep 1.


Mitochondria play a pivotal role in the life of cells, controlling diverse processes ranging from energy production to the regulation of cell death. In humans, numerous pathological conditions have been linked to mitochondrial dysfunction. Cancer, diabetes, obesity, neurodegeneration, cardiomyopathy and even aging are all associated with mitochondrial dysfunction. Over 400 mutations in mitochondrial DNA result directly in pathology and many more disorders associated with mitochondrial dysfunction arise from mutations in nuclear DNA. It is counter-intuitive then, that a class of mitochondrially defective mutants in the nematode Caenorhabditis elegans, the so called Mit (Mitochondrial) mutants, in fact live longer than wild-type animals. In this review, we will reconcile this paradox and provide support for the idea that the Mit mutants are in fact an excellent model for studying human mitochondrial associated diseases (HMADs). In the context of the 'Mitochondrial Threshold Effect Theory', we propose that the kinds of processes induced to counteract mitochondrial mutations in the Mit mutants (and which mediate their life extension), are very likely the same ones activated in many HMADs to delay disease appearance. The identification of such compensatory pathways opens a window of possibility for future preventative therapies for many HMADs. They may also provide a way of potentially extending human life span.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics*
  • Animals
  • Antioxidants / physiology
  • Caenorhabditis elegans / genetics*
  • Cell Death / genetics
  • DNA Repair / genetics
  • DNA, Mitochondrial / genetics
  • Disease Models, Animal
  • Energy Metabolism / genetics
  • Friedreich Ataxia / genetics
  • Humans
  • Iron-Binding Proteins / genetics
  • Longevity / genetics
  • Mitochondria / genetics*
  • Mitochondrial Diseases / classification
  • Mitochondrial Diseases / genetics*
  • Models, Genetic
  • Mutation
  • Oxidation-Reduction
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics


  • Antioxidants
  • DNA, Mitochondrial
  • Iron-Binding Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • frataxin