Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress.
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.
Ahmed
Shaheda
S
Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK.
Passos
João F
JF
Birket
Matthew J
MJ
Beckmann
Tina
T
Brings
Sebastian
S
Peters
Heiko
H
Birch-Machin
Mark A
MA
von Zglinicki
Thomas
T
Saretzki
Gabriele
G
D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D004272:DNA, Mitochondrial; D006861:Hydrogen Peroxide; C509186:TERT protein, human; D019098:Telomerase