Difference between revisions of "Haendeler 2009 Arterioscler Thromb Vasc Biol"
(Created page with "{{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 tra...") Ā |
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|authors=Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S Ā | |authors=Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S Ā | ||
|year=2009 | |year=2009 | ||
|abstract= | |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 | 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. | '''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 H2O2-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''. | ||
Methods and | '''Conclusion'''āMitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing | ||
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 | |||
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. | 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 | ||
Revision as of 15:06, 17 September 2010
| 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: 929-935. |
Haendeler J, Droese S, Buechner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S (2009)
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
Labels:
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
