Mitochondrially encoded methionine is inversely related to longevity in mammals

Aging Cell. 2011 Apr;10(2):198-207. doi: 10.1111/j.1474-9726.2010.00657.x. Epub 2010 Dec 29.


Methionine residues in proteins react readily with reactive oxygen species making them particularly sensitive to oxidation. However, because oxidized methionine can be reduced back in a catalyzed reaction, it has been suggested that methionine residues act as oxidant scavengers, protecting not only the proteins where they are located but also the surrounding macromolecules. To investigate whether methionine residues may be selected for or against animal longevity, we carried out a meta-examination of mitochondrial genomes from mammalian species. Our analyses unveiled a hitherto unnoticed observation: mitochondrially encoded polypeptides from short-lived species are enriched in methionine when compared with their long-lived counterparts. We show evidence suggesting that methionine addition to proteins in short-lived species, rather than methionine loss from proteins in long-lived species, is behind the reported difference in methionine usage. The inverse association between longevity and methionine, which persisted after correction for body mass and phylogenetic interdependence, was paralleled by the methionine codon AUA, but not by the codon AUG. Although nuclear encoded mitochondrial polypeptides exhibited higher methionine usage than nonmitochondrial proteins, correlation with longevity was only found within the group of those polypeptides located in the inner mitochondrial membrane. Based on these results, we propose that short-lived animals subjected to higher oxidative stress selectively accumulate methionine in their mitochondrially encoded proteins, which supports the role of oxidative damage in aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codon
  • DNA, Mitochondrial / metabolism
  • Databases, Genetic
  • Longevity / physiology*
  • Methionine / metabolism*
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Oxidation-Reduction
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism


  • Codon
  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Methionine