|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 11 March 2008
doi: 10.1242/jcs.019372
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
Related articles in JCS:
This article has been cited by other articles:
![]() |
J. C. Garbe, S. Bhattacharya, B. Merchant, E. Bassett, K. Swisshelm, H. S. Feiler, A. J. Wyrobek, and M. R. Stampfer Molecular Distinctions between Stasis and Telomere Attrition Senescence Barriers Shown by Long-term Culture of Normal Human Mammary Epithelial Cells Cancer Res., October 1, 2009; 69(19): 7557 - 7568. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Haendeler, S. Drose, N. Buchner, S. Jakob, J. Altschmied, C. Goy, I. Spyridopoulos, A. M. Zeiher, U. Brandt, and S. Dimmeler Mitochondrial Telomerase Reverse Transcriptase Binds to and Protects Mitochondrial DNA and Function From Damage Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 929 - 935. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Lee, R. Reddy, L. Barsky, J. Scholes, H. Chen, W. Shi, and B. Driscoll Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L57 - L70. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Jakob, P. Schroeder, M. Lukosz, N. Buchner, I. Spyridopoulos, J. Altschmied, and J. Haendeler Nuclear Protein Tyrosine Phosphatase Shp-2 Is One Important Negative Regulator of Nuclear Export of Telomerase Reverse Transcriptase J. Biol. Chem., November 28, 2008; 283(48): 33155 - 33161. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.H. Betts and P. Madan Permanent embryo arrest: molecular and cellular concepts Mol. Hum. Reprod., August 1, 2008; 14(8): 445 - 453. [Abstract] [Full Text] [PDF] |
||||