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Chaperoning mitochondrial permeability transition: regulation of transition pore complex by a J-protein, DnaJC15

D Sinha1, P D'Silva1

  • 1Department of Biochemistry, Indian Institute of Science, Bangalore, India.

Cell Death & Disease
|March 8, 2014
PubMed

Insights

The mitochondrial J-protein DnaJC15 regulates apoptosis by controlling the mitochondrial permeability transition pore (MPTP). Reduced DnaJC15 inhibits MPTP opening and cell death, impacting chemoresistance in ovarian cancer.

Area of Science:

  • Mitochondrial biology
  • Cell death pathways
  • Cancer research

Background:

  • Mitochondria are key regulators of apoptosis, involving transmembrane channels and death factor release.
  • Reduced DnaJC15 expression is linked to chemoresistance in ovarian cancer.
  • DnaJC15's role in cell death mechanisms remains unclear despite its involvement in protein transport.

Purpose of the Study:

  • To investigate the novel function of DnaJC15 in regulating the mitochondrial permeability transition pore (MPTP) complex.
  • To elucidate the role of DnaJC15 in apoptosis induction and its connection to cyclophilin D (CypD).

Main Methods:

  • Investigated DnaJC15's function in normal and cancer cells.
  • Examined the effect of DnaJC15 overexpression and reduction on MPTP opening and apoptosis.
  • Assessed the interaction between DnaJC15 and cyclophilin D (CypD) in relation to mitochondrial permeability transition.

Main Results:

  • Overexpression of DnaJC15 induced MPTP opening and apoptosis.
  • Reduced DnaJC15 suppressed MPTP activation, particularly upon cisplatin treatment.
  • DnaJC15 directly influences the recruitment and coupling of CypD to mitochondrial permeability transition.

Conclusions:

  • DnaJC15 plays a novel proapoptotic role by regulating the MPTP complex.
  • DnaJC15's function is linked to its interaction with CypD, a key MPTP component.
  • This study reveals a functional connection between DnaJC15 and the regulation of cell death pathways.

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