Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress

被引：372

作者：

Ahmed, Shaheda ^{[1
,2
,3
]}

Passos, Joao F. ^{[1
,2
]}

Birket, Matthew J. ^{[4
]}

Beckmann, Tina ^{[3
]}

Brings, Sebastian ^{[3
]}

Peters, Heiko ^{[5
]}

Birch-Machin, Mark A. ^{[4
]}

von Zglinicki, Thomas ^{[1
,2
]}

Saretzki, Gabriele ^{[1
,2
,3
]}

机构：

[1] Univ Newcastle, Inst Ageing & Hlth, Henry Wellcome Biogerontol Lab, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

[2] Univ Newcastle, Inst Ageing & Hlth, Ctr Integrated Syst Biol Ageing & Nutr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

[3] Univ Newcastle, Inst Ageing & Hlth, Crucible Lab, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

[4] Univ Newcastle, Sch Clin & Lab Sci, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

[5] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

来源：

JOURNAL OF CELL SCIENCE | 2008年 / 121卷 / 07期

基金：

英国生物技术与生命科学研究理事会;

关键词：

telomerase; TERT; mitochondria; oxidative stress; reactive oxygen;

D O I：

10.1242/jcs.019372

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1046 / 1053

页数：8

共 49 条

[1] Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage [J].