Prohibitin 1 modulates mitochondrial function of Stat3

Jie Han, Chunhua Yu, Rhonda F. Souza, Arianne L. Theiss

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Mitochondrial dysfunction in intestinal epithelial cells (IEC) is thought to precede the onset of inflammatory bowel diseases (IBD). Expression of Prohibitin 1 (PHB), a mitochondrial protein required for optimal electron transport chain (ETC) activity, is decreased in mucosal biopsies during active and inactive IBD. In addition to its activities as a transcription factor, Signal Transducer and Activator of Transcription 3 (Stat3) resides in the mitochondria of cells where phosphorylation at S727 is required for optimal ETC activity and protects against stress-induced mitochondrial dysfunction. Here, we show that PHB overexpression protects against mitochondrial stress and apoptosis of cultured IECs induced by TNFα, which is a pro-inflammatory cytokine involved in IBD pathogenesis. Expression of pS727-Stat3 dominant negative eliminates protection by PHB against TNFα-induced mitochondrial stress and apoptosis. PHB interacts with pS727-Stat3 in the mitochondria of cultured IECs and in colonic epithelium from wild-type mice. Our data suggest a protective role of PHB that is dependent on pS727-Stat3 to prevent mitochondrial dysfunction in IECs. Reduced levels of PHB during IBD may be an underlying factor promoting mitochondrial dysfunction of the intestinal epithelium.

Original languageEnglish (US)
Pages (from-to)2086-2095
Number of pages10
JournalCellular Signalling
Volume26
Issue number10
DOIs
StatePublished - 2014

Fingerprint

STAT3 Transcription Factor
Inflammatory Bowel Diseases
Electron Transport
Mitochondria
Apoptosis
Mitochondrial Proteins
Intestinal Mucosa
Crohn Disease
prohibitin
Transcription Factors
Epithelium
Epithelial Cells
Phosphorylation
Cytokines
Biopsy

Keywords

  • Electron transport chain
  • Intestinal epithelium
  • Mitochondria
  • Oxidative stress
  • Prohibitin
  • Stat3

ASJC Scopus subject areas

  • Cell Biology

Cite this

Prohibitin 1 modulates mitochondrial function of Stat3. / Han, Jie; Yu, Chunhua; Souza, Rhonda F.; Theiss, Arianne L.

In: Cellular Signalling, Vol. 26, No. 10, 2014, p. 2086-2095.

Research output: Contribution to journalArticle

Han, Jie ; Yu, Chunhua ; Souza, Rhonda F. ; Theiss, Arianne L. / Prohibitin 1 modulates mitochondrial function of Stat3. In: Cellular Signalling. 2014 ; Vol. 26, No. 10. pp. 2086-2095.
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