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Addressing RNA integrity to determine the impact of mitochondrial DNA mutations on brain mitochondrial function with age.
Wang W, Scheffler K, Esbensen Y, Strand JM, Stewart JB, Bjørås M, Eide L
Abstract:
.....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.
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.
PMID: 24819950
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018447/
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