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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore

Anna W C Leung1, Andrew P Halestrap

  • 1Department of Biochemistry and Bristol Heart Institute, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.

Biochimica Et Biophysica Acta
|April 15, 2008
PubMed

Insights

The mitochondrial permeability transition pore (MPTP) is crucial for cell death after ischemia. Research suggests the mitochondrial phosphate carrier (PiC), not the adenine nucleotide translocase (ANT), forms the pore, regulated by cyclophilin-D (CyP-D).

Area of Science:

  • Mitochondrial biology
  • Cell death mechanisms
  • Biochemistry

Background:

  • The mitochondrial permeability transition pore (MPTP) is implicated in cell death, particularly necrosis, and tissue injury following ischemia-reperfusion.
  • The precise molecular components of the MPTP remain elusive, hindering therapeutic development.
  • Cyclophilin-D (CyP-D) is known to be involved in MPTP opening, likely through its isomerase activity.

Purpose of the Study:

  • To critically evaluate the role of adenine nucleotide translocase (ANT) in MPTP formation.
  • To identify the primary protein component responsible for the MPTP transmembrane channel.
  • To propose a revised model for MPTP opening involving the mitochondrial phosphate carrier (PiC).

Main Methods:

  • Review of existing knockout studies and experimental evidence.
  • Analysis of the functional roles of ANT and PiC in MPTP regulation.
  • Integration of data to support a new model of MPTP assembly.

Main Results:

  • Evidence suggests ANT plays a regulatory, rather than structural, role in MPTP opening.
  • The mitochondrial phosphate carrier (PiC) is proposed as the main component forming the MPTP channel.
  • A model is presented where calcium-activated PiC conformational changes, facilitated by CyP-D, induce pore opening.

Conclusions:

  • The ANT is unlikely to form the MPTP channel but may regulate its opening.
  • The PiC is the likely structural component of the MPTP.
  • MPTP opening is a calcium-dependent process involving PiC conformational changes, CyP-D, and potentially ANT interaction.

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