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Addressing RNA integrity to determine the impact of mitochondrial DNA mutations on brain mitochondrial function with age

Lookup NU author(s): Dr Jim StewartORCiD

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Abstract

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.

Publication metadata

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

Year: 2014

Volume: 9

Issue: 5

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

URL: https://doi.org/10.1371/journal.pone.0096940

DOI: 10.1371/journal.pone.0096940

PubMed id: 24819950

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