Resolving the Enigma of the Clonal Expansion of mtDNA Deletions
Axel Kowald 1,*
and Thomas B.L. Kirkwood 1,2
and Thomas B.L. Kirkwood 1,2
1
Institute of Cell and Molecular Biosciences and Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
2
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
*
Author to whom correspondence should be addressed.
Genes 2018, 9(3), 126; https://doi.org/10.3390/genes9030126
Received: 25 January 2018 / Revised: 14 February 2018 / Accepted: 16 February 2018 / Published: 27 February 2018
(This article belongs to the Special Issue Mitochondria and Aging)
Abstract
Mitochondria are cell organelles that are special since they contain their own genetic material in the form of mitochondrial DNA (mtDNA). Damage and mutations of mtDNA are not only involved in several inherited human diseases but are also widely thought to play an important role during aging. In both cases, point mutations or large deletions accumulate inside cells, leading to functional impairment once a certain threshold has been surpassed. In most cases, it is a single type of mutant that clonally expands and out-competes the wild type mtDNA, with different mutant molecules being amplified in different cells. The challenge is to explain where the selection advantage for the accumulation comes from, why such a large range of different deletions seem to possess this advantage, and how this process can scale to species with different lifespans such as those of rats and man. From this perspective, we provide an overview of current ideas, present an update of our own proposal, and discuss the wider relevance of the phenomenon for aging. View Full-Text
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Kowald, A.; Kirkwood, T.B. Resolving the Enigma of the Clonal Expansion of mtDNA Deletions. Genes 2018, 9, 126.
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