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Mitochondrial TRAP1 regulates the unfolded protein response in the endoplasmic reticulum

Kana Takemoto1, Shingo Miyata, Hironori Takamura

  • 1Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.

Neurochemistry International
|February 23, 2011
PubMed

Insights

Mitochondria protein TRAP1 regulates endoplasmic reticulum (ER) stress response. TRAP1 knockdown activates ER stress-induced cell death pathways, revealing mitochondria

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial and endoplasmic reticulum (ER) stress independently induce cell death.
  • ER stress can cause mitochondrial dysfunction via PUMA, but mitochondrial mediators of ER dysfunction are largely unknown.

Purpose of the Study:

  • To investigate the role of mitochondrial molecules in mediating ER dysfunction.
  • To explore the connection between mitochondrial tumor necrosis factor receptor-associated protein 1 (TRAP1) and the unfolded protein response (UPR) in the ER.

Main Methods:

  • TRAP1 knockdown in human cells.
  • Analysis of caspase-4 and caspase-9 activation.
  • Measurement of GRP78/BiP and CHOP expression levels under ER stress.

Main Results:

  • TRAP1 knockdown activated ER-resident caspase-4, a marker of ER stress-induced cell death.
  • TRAP1 knockdown did not significantly increase cell death within 24 hours, as caspase-9 activation was not observed.
  • TRAP1 knockdown led to increased GRP78/BiP and decreased CHOP expression, suggesting a protective effect against ER stress.

Conclusions:

  • Mitochondrial TRAP1 is associated with the ER's unfolded protein response (UPR).
  • TRAP1 plays a role in regulating ER stress-induced cell death.
  • Mitochondria, through TRAP1, may act as regulators of the ER's UPR.

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