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Lookup NU author(s): Dr Jim StewartORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mitochondrial DNA (mtDNA) mutations can result in mitochondrial dysfunction, but emerging experimental data question the fundamental role of mtDNA mutagenesis in age-associated mitochondrial impairment. The multicopy nature of mtDNA renders the impact of a given mtDNA mutation unpredictable. In this study, we compared mtDNA stability and mtRNA integrity during normal aging. Seven distinct sites in mouse brain mtDNA and corresponding mtRNA were analyzed. Accumulation of mtDNA mutations during aging was highly site-specific. The variation in mutation frequencies overrode the age-mediated increase by more than 100-fold and aging generally did not influence mtDNA mutagenesis. Errors introduced by mtRNA polymerase were also site-dependent and up to two hundred-fold more frequent than mtDNA mutations, and independent of mtDNA mutation frequency. We therefore conclude that mitochondrial transcription fidelity limits the impact of mtDNA mutations.
Author(s): Wang W, Scheffler K, Esbensen Y, Strand JM, Stewart JB, Bjørås M, Eide L
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Online publication date: 12/05/2014
Acceptance date: 12/04/2014
Date deposited: 21/12/2020
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
PubMed id: 24819950
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