Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

Eun Jin Lee, Young Cheol Kang, Wook Ha Park, Jae Hoon Jeong, Youngmi Kim Pak

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
StatePublished - Jul 18 2014

Keywords

  • NRF-1
  • Nuclei
  • Promoter regulation
  • Repressor
  • TFAM

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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