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

ABSTRACT: 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.

SUBMITTER: Wang KZ

PROVIDER: S-EPMC4134365 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Wang Kent Z Q KZ Zhu Jianhui J Dagda Ruben K RK Uechi Guy G Cherra Salvatore J SJ Gusdon Aaron M AM Balasubramani Manimalha M Chu Charleen T CT

Mitochondrion 20140424

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, sup ...[more]

PMID: 24768991

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