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The rise and rise of mitochondrial DNA mutations

Lookup NU author(s): Dr Conor LawlessORCiD, Dr Laura Greaves, Dr Amy Reeve, Emeritus Professor Doug Turnbull, Dr Amy VincentORCiD



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


How mitochondrial DNA mutations clonally expand in an individual cell is a question that has perplexed mitochondrial biologists for decades. A growing body of literature indicates that mitochondrial DNA mutations play a major role in ageing, metabolic diseases, neurodegenerative diseases, neuromuscular disorders and cancers. Importantly, this process of clonal expansion occurs for both inherited and somatic mitochondrial DNA mutations. To complicate matters further there are fundamental differences between mitochondrial DNA point mutations and deletions, and between mitotic and post-mitotic cells, that impact this pathogenic process. These differences, along with the challenges of investigating a longitudinal process occurring over decades in humans, have so far hindered progress towards understanding clonal expansion. Here we summarize our current understanding of the clonal expansion of mitochondrial DNA mutations in different tissues and highlight key unanswered questions. We then discuss the various existing biological models, along with their advantages and disadvantages. Finally, we explore what has been achieved with mathematical modelling so far and suggest future work to advance this important area of research.

Publication metadata

Author(s): Lawless C, Greaves L, Reeve AK, Turnbull DM, Vincent AE

Publication type: Article

Publication status: Published

Journal: Open biology

Year: 2020

Volume: 10

Issue: 5

Online publication date: 20/05/2020

Acceptance date: 23/04/2020

Date deposited: 01/06/2020

ISSN (electronic): 2046-2441

Publisher: Royal Society


DOI: 10.1098/rsob.200061

PubMed id: 32428418


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