ERK-mediated phosphorylation of TFAM downregulates mitochondrial transcription: Implications for Parkinson's disease

Kent Z.Q. Wang, Jianhui Zhu, Ruben K. Dagda, Guy Uechi, Salvatore J. Cherra, Aaron M. Gusdon, Manimalha Balasubramani, Charleen T. Chu

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, which is downregulated by extracellular signal-regulated protein kinases (ERK1/2) in cells treated chronically with the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+). We utilized mass spectrometry to identify ERK1/2-dependent TFAM phosphorylation sites. Mutation of TFAM at serine 177 to mimic phosphorylation recapitulated the effects of MPP+ in decreasing the binding of TFAM to the light strand promoter, suppressing mitochondrial transcription. Mutant TFAM was unable to affect respiratory function or rescue the effects of MPP+ on respiratory complexes. These data disclose a novel mechanism by which ERK1/2 regulates mitochondrial function through direct phosphorylation of TFAM.

Original languageEnglish
Pages (from-to)132-140
Number of pages9
StatePublished - Jul 2014

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health ( R01 AG026389, R01 NS065789 and K18 DC009120 ). The Genomics and Proteomics Core Laboratories and Biomedical Mass Spectrometry Center were supported in part by UL1 RR024153, UL1 TR000005 and P30 CA047904. The funding agencies were not involved in the study design, collection and interpretation of the data, writing of the report, or the decision to submit for publication.


  • MAP kinases
  • Mitochondrial biogenesis
  • MtDNA
  • Parkinson disease
  • Phosphorylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology


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