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STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization

Hyunmi Kim1,2, Soo Jung Park1, Ilo Jou1

  • 1Department of Pharmacology, Inflammaging Translational Research Center, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon 16499, Korea.

Iscience
|September 6, 2022
PubMed

Insights

Nuclear transcription factors (TFs) in mitochondria regulate key cell processes. We found STAT6 in the outer mitochondrial membrane inhibits fusion, revealing its role in mitochondrial dynamics and response to hypoxia.

Area of Science:

  • Mitochondrial biology
  • Cellular signaling
  • Molecular mechanisms of mitochondrial dynamics

Background:

  • Nuclear transcription factors (TFs) are known to regulate mitochondrial functions like apoptosis and respiration.
  • The precise roles and mechanisms of mitochondrial dynamics controlled by mitochondria-localized nuclear TFs remain incompletely understood.

Purpose of the Study:

  • To investigate the function and mechanism of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs.
  • To identify specific TFs involved in regulating mitochondrial fusion and fission.

Main Methods:

  • Identification of STAT6 as a mitochondrial protein.
  • Localization of STAT6 to the outer mitochondrial membrane (OMM).
  • Assessment of STAT6's effect on mitochondrial fusion, specifically MFN2 dimerization, under hypoxic conditions.

Main Results:

  • STAT6 was identified as a protein localized to the OMM.
  • STAT6 was found to inhibit mitochondrial fusion by preventing MFN2 dimerization.
  • Mitochondrial accumulation of STAT6 was observed under hypoxic conditions, indicating its role in regulating mitochondrial dynamics.

Conclusions:

  • STAT6 plays a critical role in regulating mitochondrial dynamics, particularly mitochondrial fusion.
  • STAT6 acts as a key regulator of mitochondrial fusion/fission mechanisms in response to cellular stress like hypoxia.
  • This study elucidates a novel function of a nuclear TF in the mitochondria, impacting mitochondrial structure and function.
Keywords:
Biological sciencesMolecular biologyMolecular interactionNatural sciences

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