Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8399431 | Mitochondrion | 2014 | 9 Pages |
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.
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Authors
Kent Z.Q. Wang, Jianhui Zhu, Ruben K. Dagda, Guy Uechi, Salvatore J. III, Aaron M. Gusdon, Manimalha Balasubramani, Charleen T. Chu,