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Mitochondrial dysfunction leads to telomere attrition and genomic instability

Mitochondrial dysfunction leads to telomere attrition and genomic instability
Mitochondrial dysfunction leads to telomere attrition and genomic instability
Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging-associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging-associated pathologies.

apoptosis, mitochondria, mouse, oxidative stress, telomere
1474-9718
40-46
Liu, Lin
51bc0635-5ce3-4ade-9edf-624ec8a1750b
Trimarchi, James R.
dc15c269-2b07-41fb-b3e5-a9ac457c7994
Smith, Peter J. S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Keefe, David L.
a1d0a08b-d76a-4d64-b2dd-4d1a5fc04451
Liu, Lin
51bc0635-5ce3-4ade-9edf-624ec8a1750b
Trimarchi, James R.
dc15c269-2b07-41fb-b3e5-a9ac457c7994
Smith, Peter J. S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Keefe, David L.
a1d0a08b-d76a-4d64-b2dd-4d1a5fc04451

Liu, Lin, Trimarchi, James R., Smith, Peter J. S. and Keefe, David L. (2002) Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell, 1 (1), 40-46. (doi:10.1046/j.1474-9728.2002.00004.x).

Record type: Article

Abstract

Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging-associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging-associated pathologies.

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More information

Published date: October 2002
Keywords: apoptosis, mitochondria, mouse, oxidative stress, telomere

Identifiers

Local EPrints ID: 188837
URI: http://eprints.soton.ac.uk/id/eprint/188837
ISSN: 1474-9718
PURE UUID: 2fc14a5e-664b-4fe9-b8de-664af91da6c3
ORCID for Peter J. S. Smith: ORCID iD orcid.org/0000-0003-4400-6853

Catalogue record

Date deposited: 17 Jun 2011 12:28
Last modified: 26 Nov 2021 02:57

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Contributors

Author: Lin Liu
Author: James R. Trimarchi
Author: David L. Keefe

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