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First published online 11 March 2008
doi: 10.1242/jcs.019372
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Research Article |
1 Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
2 Henry Wellcome Biogerontology Laboratory and Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
3 School of Clinical and Laboratory Sciences, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
4 Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
* Author for correspondence (e-mail: t.vonzglinicki{at}ncl.ac.uk)
Accepted 17 January 2008
Telomerase is a ribonucleoprotein that counteracts telomere shortening and can immortalise human cells. There is also evidence for a telomere-independent survival function of telomerase. However, its mechanism is not understood. We show here that TERT, the catalytic subunit of human telomerase, protects human fibroblasts against oxidative stress. While TERT maintains telomere length under standard conditions, telomeres under increased stress shorten as fast as in cells without active telomerase. This is because TERT is reversibly excluded from the nucleus under stress in a dose- and time-dependent manner. Extranuclear telomerase colocalises with mitochondria. In TERT-overexpressing cells, mtDNA is protected, mitochondrial membrane potential is increased and mitochondrial superoxide production and cell peroxide levels are decreased, all indicating improved mitochondrial function and diminished retrograde response. We propose protection of mitochondria under mild stress as a novel function of TERT.
Key words: Telomerase, TERT, Mitochondria, Oxidative stress, Reactive oxygen
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