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Resolving the Enigma of the Clonal Expansion of mtDNA Deletions

Lookup NU author(s): Dr Axel Kowald, Emeritus Professor Thomas Kirkwood



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 by the authors. Licensee MDPI, Basel, Switzerland. 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.

Publication metadata

Author(s): Kowald A, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: Genes

Year: 2018

Volume: 9

Issue: 3

Online publication date: 27/02/2018

Acceptance date: 16/02/2018

Date deposited: 19/03/2018

ISSN (print): 2073-4425

ISSN (electronic): 2073-4425

Publisher: MDPI AG


DOI: 10.3390/genes9030126


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