The import of the transcription factor STAT3 into mitochondria depends on GRIM-19, a component of the electron transport chain

J Biol Chem. 2013 Feb 15;288(7):4723-32. doi: 10.1074/jbc.M112.378984. Epub 2012 Dec 27.


The signal transducer and activator of transcription 3 (STAT3), a nuclear transcription factor, is also present in mitochondria and regulates cellular respiration in a transcriptional-independent manner. The mechanism of STAT3 import into mitochondria remains obscure. In this report we show that mitochondrial-localized STAT3 resides in the inner mitochondrial membrane. In vitro import studies show that the gene associated with retinoid interferon induced cell mortality 19 (GRIM-19), a complex I subunit that acts as a chaperone to recruit STAT3 into mitochondria. In addition, GRIM-19 enhances the integration of STAT3 into complex I. A S727A mutation in STAT3 reduces its import and assembly even in the presence of GRIM-19. Together, our studies unveil a novel chaperone function for GRIM-19 in the recruitment of STAT3 into mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Biological Transport
  • Electron Transport Complex I / metabolism*
  • Electron Transport*
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Membranes / metabolism*
  • Models, Biological
  • Molecular Chaperones / metabolism*
  • NADH, NADPH Oxidoreductases / metabolism*
  • Phosphorylation
  • Rabbits
  • Rats
  • STAT3 Transcription Factor / metabolism*


  • Apoptosis Regulatory Proteins
  • Molecular Chaperones
  • STAT3 Transcription Factor
  • NADH, NADPH Oxidoreductases
  • NDUFA13 protein, human
  • Electron Transport Complex I
  • Ndufa13 protein, rat