title: Muscle-specific overexpression of the catalytic subunit of DNA polymerase γ induces pupal lethality in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Facultad de Medicina CIBERER ISCIII, Universidad Autónoma de Madrid, Madrid, Spain. fmartinez@h12o.es
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Azorín
authors.forename: Manuel
authors.initials: M
authors.lastname: Calleja
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández-Sierra
authors.forename: Carol L
authors.initials: CL
authors.lastname: Farr
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Kaguni
authors.forename: Rafael
authors.initials: R
authors.lastname: Garesse
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D015139:Blotting, Southern; D020134:Catalytic Domain / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000502:physiology*; D060227:Imaginal Discs / Q000166:cytology; D015151:Immunoblotting; D009132:Muscles / Q000378:metabolism*; D011679:Pupa / Q000201:enzymology; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D029721:Drosophila Proteins; C489029:TFAM protein, Drosophila; D014157:Transcription Factors; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase