Stat3 binds to mtDNA and regulates mitochondrial gene expression in keratinocytes.

Published

Journal Article

The nuclear transcription factor signal transducer and activator of transcription 3 (Stat3) has recently been reported to have a localized mitochondrial regulatory function. Current data suggest that mitochondrial Stat3 (mitoStat3) is necessary for maximal mitochondrial activity and for Ras-mediated transformation independent of Stat3 nuclear activity. We have previously shown that Stat3 has a pivotal role in epithelial carcinogenesis. Therefore, the aim of the current study was to determine the role of mitoStat3 in epidermal keratinocytes. Herein, we show that normal and neoplastic keratinocytes contain a pool of mitoStat3. EGF and 12-O-tetradecanoylphorbol-13-acetate induce Stat3 mitochondrial translocation mediated through the phosphorylation of Stat3 at Ser727. In addition, we report that mitoStat3 binds mtDNA and associates with the mitochondrial transcription factor A. Furthermore, Stat3 ablation resulted in an increase of mitochondrial-encoded gene transcripts. An increase in key nuclear-encoded metabolic genes, PGC-1α and NRF-1, was also observed in Stat3-null keratinocytes; however, no changes in nuclear-encoded electron transport chain gene transcripts or mtDNA copy number were observed. Collectively, our findings suggest a heretofore-unreported function for mitoStat3 as a potential mitochondrial transcription factor in keratinocytes. This mitoStat3-mtDNA interaction may represent an alternate signaling pathway that could alter mitochondrial function and biogenesis and have a role in tumorigenesis.

Full Text

Duke Authors

Cited Authors

  • Macias, E; Rao, D; Carbajal, S; Kiguchi, K; DiGiovanni, J

Published Date

  • July 2014

Published In

Volume / Issue

  • 134 / 7

Start / End Page

  • 1971 - 1980

PubMed ID

  • 24496235

Pubmed Central ID

  • 24496235

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

Digital Object Identifier (DOI)

  • 10.1038/jid.2014.68

Language

  • eng

Conference Location

  • United States