How is mutant mitochondrial DNA clonally amplified? Much new evidence, still no answers.
Twenty years have passed since Kadenbach and Müller-Höcker first proposed that the age-related accumulation of mutant mitochondrial DNA is caused by its clonal expansion, rather than by a "vicious cycle" of de novo mutational events caused by the disruptive metabolic impact of prior ones. Proof that they were correct emerged rapidly (though recognition of this was much slower); however, the mechanism underlying this selective advantage remained obscure. Numerous hypotheses were advanced during the 1990s, but proved hard to test. A wealth of data has been published very recently that bears on this question. While these reports surely bring us closer to an understanding of this phenomenon, and thus probably to a better understanding of how it might be combated or even reversed, they currently raise more questions than they answer.
de Grey
Aubrey D N J
AD
SENS Foundation, Cambridge, United Kingdom. aubrey@sens.org
D000375:Aging; D000818:Animals; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D013234:Stem Cells / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D004272:DNA, Mitochondrial; D013481:Superoxides