Phosphorylation of mitochondrial transcription factor B2 controls mitochondrial DNA binding and transcription

Biochem Biophys Res Commun. 2020 Jul 30;528(3):580-585. doi: 10.1016/j.bbrc.2020.05.141. Epub 2020 Jun 3.


Mammalian cells contain genetic information in two compartments, the nucleus and the mitochondria. Mitochondrial gene expression must be coordinated with nuclear gene expression to respond to cellular energetic needs. To gain insight into the coordination between the nucleus and mitochondria, there is a need to understand the regulation of transcription of mitochondrial DNA (mtDNA). Reversible protein post-translational modifications of the mtDNA transcriptional machinery may be one way to control mtDNA transcription. Here we focus on a member of the mtDNA transcription initiation complex, mitochondrial transcription factor B2 (TFB2M). TFB2M melts mtDNA at the promoter to allow the RNA polymerase (POLRMT) to access the DNA template and initiate transcription. Three phosphorylation sites have been previously identified on TFB2M by mass spectrometry: threonine 184, serine 197, and threonine 313. Phosphomimetics were established at these positions. Proteins were purified and analyzed for their ability to bind mtDNA and initiate transcription in vitro. Our results indicate phosphorylation at threonine 184 and threonine 313 impairs promoter binding and prevents transcription. These findings provide a potential regulatory mechanism of mtDNA transcription and help clarify the importance of protein post-translational modifications in mitochondrial function.

Keywords: Mitochondrial DNA; Mitochondrial transcription factor B2 (TFB2M); Phosphorylation; Transcription regulation.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism*
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / metabolism
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Methyltransferases / chemistry
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Molecular Mimicry / genetics
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcription Initiation Site
  • Transcription, Genetic


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Transcription Factors
  • Methyltransferases
  • TFB2M protein, human
  • DNA-Directed RNA Polymerases
  • POLRMT protein, human