Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases

Lancet. 1989 Mar 25;1(8639):642-5. doi: 10.1016/s0140-6736(89)92145-4.


The human mitochondrial genome is very small and economically packed; the expression of the whole genome is essential for the maintenance of mitochondrial bioenergetic function. Mutation occurs at a much higher rate in the mitochondrial DNA (mtDNA) than in chromosomal DNA. Transient heteroplasmy of mtDNA occurs after a mutational event; the random pattern of cytoplasmic segregation that occurs during subsequent growth gives rise to a mosaic of cells. The variable proportion of mutant mitochondrial genomes per cell results in cells with a range of bioenergetic capacities. It is proposed that the accumulation of mitochondrial mutations and the subsequent cytoplasmic segregation of these mutations during life is an important contributor both to the ageing process and to several human degenerative diseases. Replacement therapy and pharmacological support may be possible for the amelioration of such disorders by means of appropriate redox compounds. Moreover, new compounds with desired redox potentials can be rationally designed for clinical use.

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Bone Diseases / genetics*
  • Bone Diseases / metabolism
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Female
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Mosaicism
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Mutation*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Yeasts / genetics
  • Yeasts / metabolism


  • DNA, Mitochondrial