Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development

Cristina Adán, Yuichi Matsushima, Rosana Hernández-Sierra, Raquel Marco-Ferreres, Miguel Ángel Fernández-Moreno, Emiliano González-Vioque, Manuel Calleja, Juan J. Aragón, Laurie S. Kaguni, Rafael Garesse

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Characterization of the basal transcription machinery of mitochondrial DNA (mtDNA) is critical to understand mitochondrial pathophysiology. In mammalian in vitro systems, mtDNA transcription requires mtRNA polymerase, transcription factor A (TFAM), and either transcription factor B1 (TFB1M) or B2 (TFB2M). We have silenced the expression of TFB2M by RNA interference in Drosophila melanogaster. RNA interference knockdown of TF2BM causes lethality by arrest of larval development. Molecular analysis demonstrates that TF2BM is essential for mtDNA transcription during Drosophila development and is not redundant with TFB1M. The impairment of mtDNA transcription causes a dramatic decrease in oxidative phosphorylation and mitochondrial ATP synthesis in the long-lived larvae, and a metabolic shift to glycolysis, which partially restores ATP levels and elicits a compensatory response at the nuclear level that increases mitochondrial mass. At the cellular level, the mitochondrial dysfunction induced by TFB2M knockdown causes a severe reduction in cell proliferation without affecting cell growth, and increases the level of apoptosis. In contrast, cell differentiation and morphogenesis are largely unaffected. Our data demonstrate the essential role of TFB2M in mtDNA transcription in a multicellular organism, and reveal the complex cellular, biochemical, and molecular responses induced by impairment of oxidative phosphorylation during Drosophila development.

Original languageEnglish
Pages (from-to)12333-12342
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number18
DOIs
Publication statusPublished - May 2 2008

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Transcription
Drosophila melanogaster
Mitochondrial DNA
Transcription Factors
Oxidative Phosphorylation
RNA Interference
Drosophila
Adenosine Triphosphate
RNA
Cell proliferation
Cell growth
Glycolysis
Morphogenesis
Machinery
Larva
Cell Differentiation
Cell Proliferation
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Adán, C., Matsushima, Y., Hernández-Sierra, R., Marco-Ferreres, R., Fernández-Moreno, M. Á., González-Vioque, E., ... Garesse, R. (2008). Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. Journal of Biological Chemistry, 283(18), 12333-12342. https://doi.org/10.1074/jbc.M801342200

Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. / Adán, Cristina; Matsushima, Yuichi; Hernández-Sierra, Rosana; Marco-Ferreres, Raquel; Fernández-Moreno, Miguel Ángel; González-Vioque, Emiliano; Calleja, Manuel; Aragón, Juan J.; Kaguni, Laurie S.; Garesse, Rafael.

In: Journal of Biological Chemistry, Vol. 283, No. 18, 02.05.2008, p. 12333-12342.

Research output: Contribution to journalArticle

Adán, C, Matsushima, Y, Hernández-Sierra, R, Marco-Ferreres, R, Fernández-Moreno, MÁ, González-Vioque, E, Calleja, M, Aragón, JJ, Kaguni, LS & Garesse, R 2008, 'Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development', Journal of Biological Chemistry, vol. 283, no. 18, pp. 12333-12342. https://doi.org/10.1074/jbc.M801342200
Adán C, Matsushima Y, Hernández-Sierra R, Marco-Ferreres R, Fernández-Moreno MÁ, González-Vioque E et al. Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. Journal of Biological Chemistry. 2008 May 2;283(18):12333-12342. https://doi.org/10.1074/jbc.M801342200
Adán, Cristina ; Matsushima, Yuichi ; Hernández-Sierra, Rosana ; Marco-Ferreres, Raquel ; Fernández-Moreno, Miguel Ángel ; González-Vioque, Emiliano ; Calleja, Manuel ; Aragón, Juan J. ; Kaguni, Laurie S. ; Garesse, Rafael. / Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 18. pp. 12333-12342.
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