MUSCLE-SPECIFIC OVEREXPRESSION OF THE CATALYTIC SUBUNIT OF DNA POLYMERASE γ INDUCES PUPAL LETHALITY IN Drosophila melanogaster

被引:1
|
作者
Martinez-Azorin, Francisco [1 ,2 ]
Calleja, Manuel [3 ]
Hernandez-Sierra, Rosana [1 ,4 ]
Farr, Carol L. [5 ,6 ]
Kaguni, Laurie S. [5 ,6 ]
机构
[1] Univ Autonoma Madrid, Dept Bioquim, Fac Med CIBERER ISCIII, Inst Invest Biomed Alberto Sols CSIC, Madrid, Spain
[2] Hosp 12 Octubre I 12, CIBERER ISCIII, Lab Enfermedades Mitocondriales, Inst Invest, E-28041 Madrid, Spain
[3] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa CSIC, Madrid, Spain
[4] Hosp 12 Octubre I 12, Inst Invest, Lab Biogenesis Mitocondrial, E-28041 Madrid, Spain
[5] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA
[6] Michigan State Univ, Ctr Mitochondrial Sci & Med, E Lansing, MI 48824 USA
基金
美国国家卫生研究院;
关键词
apoptosis; DNA polymerase gamma; Drosophila melanogaster; mitochondria; oxidative phosphorylation; MITOCHONDRIAL TRANSCRIPTION FACTOR; ACCESSORY SUBUNIT; MTDNA POLYMERASE; CELL-DEATH; FACTOR-A; EXPRESSION; APOPTOSIS; DEPLETION; DISEASE; EMBRYOS;
D O I
10.1002/arch.21101
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We show the physiological effects and molecular characterization of overexpression of the catalytic core of mitochondrial DNA (mtDNA) polymerase (pol -) in muscle of Drosophila melanogaster. Muscle-specific overexpression of pol - using the UAS/GAL4 (where UAS is upstream activation sequence) system produced more than 90% of lethality at the end of pupal stage at 25 degrees C, and the survivor adult flies showed a significant reduction in life span. The survivor flies displayed a decreased mtDNA level that is accompanied by a corresponding decrease in the levels of the nucleoid-binding protein mitochondrial transcription factor A (mtTFA). Furthermore, an increase in apoptosis is detected in larvae and adults overexpressing pol -. We suggest that the pupal lethality and reduced life span of survivor adult flies are both caused mainly by massive apoptosis of muscle cells induced by mtDNA depletion. (C) 2013 Wiley Periodicals, Inc.
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页码:127 / 137
页数:11
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