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Updated: Jun 14, 2025

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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Mitochondrial permeability transition mediated by MTCH2 and F-ATP synthase contributes to ferroptosis defense

Lishu Guo1

  • 1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

FEBS Letters
|September 3, 2024
PubMed

Insights

Mitochondrial carrier homolog 2 (MTCH2) links the mitochondrial permeability transition pore (PTP) and outer membrane permeabilization (MOMP). This interaction regulates ferroptosis defense, highlighting a new role for PTP in cell death pathways.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Biochemistry

Background:

  • The mitochondrial permeability transition pore (PTP) opening leads to mitochondrial outer membrane permeabilization (MOMP) and cell death, but the mechanism is not fully understood.
  • Mitochondrial carrier homolog 2 (MTCH2) is known to mediate MOMP by recruiting tBID.
  • Cyclophilin D (CyPD) is a key regulator of PTP opening.

Purpose of the Study:

  • To elucidate the mechanism by which PTP opening induces MOMP.
  • To investigate the role of MTCH2 in coordinating PTP and MOMP.
  • To determine the involvement of mitochondrial permeability transition in ferroptosis.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Cell viability assays to assess ferroptosis.
  • Gene knockdown experiments (CyPD, MTCH2, subunit j).

Main Results:

  • MTCH2 binds to CyPD and promotes F-ATP synthase dimerization through subunit j.
  • The MTCH2-CyPD-subunit j complex coordinates PTP and MOMP.
  • Knockdown of CyPD, MTCH2, or subunit j sensitizes cells to ferroptosis, which is inhibited by MitoTEMPO.

Conclusions:

  • MTCH2, CyPD, and F-ATP synthase subunit j form a complex that links PTP and MOMP.
  • Mitochondrial permeability transition is a critical mediator of ferroptosis defense.
Keywords:
F‐ATP synthasecyclophilin Dferroptosismitochondrial carrier homolog 2mitochondrial permeability transition

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