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Transcription could be the key to the selection advantage of mitochondrial deletion mutants in aging

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

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Abstract

The mitochondrial theory of aging is widely popular but confronted by several apparent inconsistencies. On the one hand, mitochondrial energy production is of central importance to the health and proper functioning of cells, and single-cell studies have shown that mtDNA deletion mutants accumulate in a clonal fashion in various mammalian species, displacing the wild-type mtDNAs. On the other hand, no explanation exists yet for the clonal expansion of mtDNA mutants that is compatible with experimental observations. We present here a new idea based on the distinctive connection between transcription and replication of metazoan mtDNA. Bioinformatic analysis of mtDNA deletion spectra strongly supports the predictions of this hypothesis and identifies specific candidates for proteins involved in transcriptional control of mtDNA replication. Computer simulations show the mechanism to be compatible with the available data from short-and long-lived mammalian species.


Publication metadata

Author(s): Kowald A, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: Proceedings of the National Academy of Sciences of the United States of America

Year: 2014

Volume: 111

Issue: 8

Pages: 2972-2977

Print publication date: 03/02/2014

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences

URL: http://dx.doi.org/10.1073/pnas.1314970111

DOI: 10.1073/pnas.1314970111


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