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Haendeler 2009 Arterioscler Thromb Vasc Biol

From Bioblast
Publications in the MiPMap
Haendeler J, Dröse S, Büchner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S (2009) Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arterioscler Thromb Vasc Biol 29:929-35.

» PMID: 19265030 Open Access

Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S (2009) Arterioscler Thromb Vasc Biol

Abstract: Objective—The enzyme telomerase and its catalytic subunit the telomerase reverse transcriptase (TERT) are important for maintenance of telomere length in the nucleus. Recent studies provided evidence for a mitochondrial localization of TERT. Therefore, we investigated the exact localization of TERT within the mitochondria and its function.

Methods and Results—Here, we demonstrate that TERT is localized in the matrix of the mitochondria. TERT binds to mitochondrial DNA at the coding regions for ND1 and ND2. Binding of TERT to mitochondrial DNA protects against ethidium bromide–induced damage. TERT increases overall respiratory chain activity, which is most pronounced at Complex I and dependent on the reverse transcriptase activity of the enzyme. Moreover, mitochondrial reactive oxygen species are increased after genetic ablation of TERT by shRNA. Mitochondrially targeted TERT and not wild-type TERT revealed the most prominent protective effect on H2O2-induced apoptosis. Lung fibroblasts from 6-month-old TERT-/- mice (F2 generation) showed increased sensitivity toward UVB radiation and heart mitochondria exhibited significantly reduced respiratory chain activity already under basal conditions, demonstrating the protective function of TERT in vivo.

Conclusion—Mitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stress–induced damage. Keywords: Aging, Apoptosis, Mitochondrial functions, Mitochondrial DNA, Reactive oxygen species, Telomerase reverse transcriptase

O2k-Network Lab: NL Nijmegen Brandt U, DE Frankfurt Droese S, DE Duesseldorf Haendeler J

Labels: MiParea: Respiration, mtDNA;mt-genetics  Pathology: Cancer  Stress:Oxidative stress;RONS  Organism: Human, Mouse  Tissue;cell: Heart, Endothelial;epithelial;mesothelial cell, Fibroblast  Preparation: Intact cells, Enzyme 

Regulation: Substrate  Coupling state: OXPHOS 

HRR: Oxygraph-2k