Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Facultad de Medicina CIBERER ISCIII, Universidad Autónoma de Madrid, Madrid, Spain.
Arch Insect Biochem Physiol. 2013 Jul;83(3):127-37. doi: 10.1002/arch.21101. Epub 2013 May 31.
We show the physiological effects and molecular characterization of overexpression of the catalytic core of mitochondrial DNA (mtDNA) polymerase (pol γ-α) in muscle of Drosophila melanogaster. Muscle-specific overexpression of pol γ-α 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°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 γ-α. 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.
我们展示了线粒体 DNA（mtDNA）聚合酶（pol γ-α）催化核心在黑腹果蝇肌肉中的过表达的生理效应和分子特征。使用 UAS/GAL4（其中 UAS 是上游激活序列）系统在肌肉中特异性过表达 pol γ-α，在 25°C 时，在蛹期末产生超过 90%的致死率，存活下来的成年果蝇的寿命明显缩短。存活下来的果蝇表现出 mtDNA 水平降低，同时核蛋白结合蛋白线粒体转录因子 A（mtTFA）的水平也相应降低。此外，在过表达 pol γ-α的幼虫和成虫中检测到凋亡增加。我们认为，蛹期致死和存活成年果蝇寿命缩短主要是由 mtDNA 耗竭诱导的肌肉细胞大量凋亡引起的。
