Difference between revisions of "Haendeler 2009 Arterioscler Thromb Vasc Biol"
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{{Publication | {{Publication | ||
|title=Haendeler J, Drƶse S, BĆ¼chner 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 | |title=Haendeler J, Drƶse S, BĆ¼chner 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. | ||
|authors=Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S Ā | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19265030 PMID: 19265030 Open Access] | ||
|authors=Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S | |||
|year=2009 | |year=2009 | ||
|abstract= | |journal=Arterioscler Thromb Vasc Biol | ||
maintenance of telomere length in the nucleus. Recent studies provided evidence for a mitochondrial localization of | |abstract='''Objective'''āThe 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. | ||
TERT. Therefore, we investigated the exact localization of TERT within the mitochondria and its function. | Ā | ||
Methods and | '''Methods and Results'''āHere, 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 bromideāinduced 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 H<sub>2</sub>O<sub>2</sub>-induced apoptosis. Lung fibroblasts from 6-month-old TERT<sup>-/-</sup>Ā 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''. | ||
mitochondrial DNA at the coding regions for ND1 and ND2. Binding of TERT to mitochondrial DNA protects against | Ā | ||
ethidium bromideāinduced damage. TERT increases overall respiratory chain activity, which is most pronounced at | '''Conclusion'''āMitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stressāinduced damage. | ||
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 | |||
significantly reduced respiratory chain activity already under basal conditions, demonstrating the protective function of | |||
TERT in vivo. | |||
respiratory chain activity and protecting against oxidative stressāinduced damage. | |||
|keywords=Aging,Ā Apoptosis,Ā Mitochondrial functions,Ā Mitochondrial DNA,Ā Reactive oxygen species,Ā Telomerase reverse transcriptase | |keywords=Aging,Ā Apoptosis,Ā Mitochondrial functions,Ā Mitochondrial DNA,Ā Reactive oxygen species,Ā Telomerase reverse transcriptase | ||
| | |mipnetlab=NL Nijmegen Brandt U, DE Frankfurt Droese S, DE Duesseldorf Haendeler J | ||
|discipline=Mitochondrial Physiology, Biomedicine | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, mtDNA;mt-genetics | |||
|diseases=Cancer | |||
|injuries=Oxidative stress;RONS | |||
|organism=Human, Mouse | |||
|tissues=Heart, Endothelial;epithelial;mesothelial cell, Fibroblast | |||
|preparations=Intact cells, Enzyme | |||
|topics=Substrate | |||
|couplingstates=OXPHOS | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
| | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
Latest revision as of 10:26, 27 March 2018
| Haendeler J, Drƶse S, BĆ¼chner 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. |
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: ObjectiveāThe 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 ResultsāHere, 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 bromideāinduced 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.
ConclusionāMitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stressāinduced damage. ā¢ Keywords: Aging, Apoptosis, Mitochondrial functions, Mitochondrial DNA, Reactive oxygen species, Telomerase reverse transcriptase
ā¢ 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
