Abstract
Mitochondrial protein synthesis is critical in biogenesis of electron transport chain and maintenance of mitochondrial function. Mitochondrial transcription factor B1 (TFB1M), an in vitro mitochondrial transcription activator, has been identified as an important mitochondrial translation regulator in vivo. To elucidate its physiological function, we generated and characterized Drosophila TFB1M mutants. Although TFB1M mutants showed normal development, decreased ATP level and reduced activity of complex IV, the last enzyme in electron transport chain, were observed in the indirect flight muscle of TFB1M mutants. Moreover, TFB1M mutants showed an increased sensitivity to oxidative stress and a significant accumulation of oxidative damage. In addition to these TFB1M mutant phenotypes, over-expression of TFB1M substantially ameliorated mitochondria dysfunction and the disease-related phenotypes in Drosophila Parkinson’s disease (PD) models. These data demonstrate the role of TFB1M in maintaining mitochondrial function and oxidative stress resistance.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adán C, Matsushima Y, Hernández-Sierra R, Marco-Ferreres R, Fernández-Moreno MA, et al. (2008) Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. J. Biol. Chem. 283: 12333–12342.
Cha GH, Kim S, Park J, Lee E, Kim M, et al. (2005) Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc. Natl. Acad. Sci. USA 102: 10345–10350.
Clark IE, Dodson MW, Jiang CG, Cao JH, Huh JR, et al. (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441: 1162–1166.
Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG and Gustafsson CM (2002) Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat. Genet. 31: 289–294.
Halliwell B and Chirico S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am. J. Clin. Nutr. 57: 715S–724S; discussion 724S–725S.
Henchcliffe C and Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat. Clin. Pract. Neurol. 4: 600–609.
Keeney PM, Xie J, Capaldi RA and Bennett JP (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J. Neurosci. 26: 5256–5264.
Lee JH, Koh H, Kim M, Kim Y, Lee SY, et al. (2007) Energy-dependent regulation of cell structure by AMP-activated protein kinase. Nature 447: 1017–1019.
Matsushima Y, Garesse R and Kaguni LS (2004) Drosophila mitochondrial transcription factor B2 regulates mitochondrial DNA copy number and transcription in schneider cells. J. Biol. Chem. 279: 26900–26905.
Matsushima Y, Adan C, Garesse R and Kaguni LS (2005) Drosophila mitochondrial transcription factor B1 modulates mitochondrial translation but not transcription or DNA copy number in Schneider cells. J. Biol. Chem. 280: 16815–16820.
McCulloch V, Seidel-Rogol BL and Shadel GS (2002) A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine. Mol. Cell. Biol. 22: 1116–1125.
Metodiev MD, Lesko N, Park CB, Camara Y, Shi YH, et al. (2009) Methylation of 12S rRNA Is Necessary for In Vivo Stability of the Small Subunit of the Mammalian Mitochondrial Ribosome. Cell Metab. 9: 386–397.
Park CB, Asin-Cayuela J, Camara Y, Shi YH, Pellegrini M, et al. (2007) MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130: 273–285.
Park J, Kim Y and Chung J (2009) Mitochondrial dysfunction and Parkinson’s disease genes: insights from Drosophila. Dis. Model Mech. 2: 336–340.
Park J, Lee SB, Lee S, Kim Y, Song S, et al. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441: 1157–1161.
Parker WD, Parks JK and Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res. 1189: 215–218.
Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol. Rev. 88: 611–638.
Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P and Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J. Neurochem. 54: 823–827.
Yang YF, Gehrke S, Imai Y, Huang ZN, Ouyang Y, et al. (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl. Acad. Sci. USA 103: 10793–10798.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, H., Kim, M.J., Jeong, J.E. et al. Mitochondrial transcription factor B1 is required for mitochondrial function and oxidative stress resistance in Drosophila . Genes Genom 32, 455–461 (2010). https://doi.org/10.1007/s13258-010-0052-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13258-010-0052-3