Muscle-specific overexpression of the catalytic subunit of DNA polymerase γ induces pupal lethality in Drosophila melanogaster

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis / genetics*
  • Apoptosis / physiology
  • Blotting, Southern
  • Catalytic Domain / genetics
  • DNA Polymerase gamma
  • DNA, Mitochondrial / metabolism*
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / enzymology*
  • Gene Expression Regulation / physiology*
  • Imaginal Discs / cytology
  • Immunoblotting
  • Muscles / metabolism*
  • Pupa / enzymology
  • Survival Analysis
  • Transcription Factors / metabolism


  • DNA, Mitochondrial
  • Drosophila Proteins
  • TFAM protein, Drosophila
  • Transcription Factors
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase