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Updated: Aug 17, 2026

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

Published on: June 1, 2022

Effects of decreasing mitochondrial volume on the regulation of the permeability transition pore

Véronique Nogueira1, Anne Devin, Ludivine Walter

  • 1INSERM E-0221 Bioénergétique Fondamentale et Appliquée, Université J. Fourier-BP53, F-38041 Grenoble Cedex, France.

Journal of Bioenergetics and Biomembranes
|May 21, 2005
PubMed

Insights

Mitochondrial volume significantly impacts the permeability transition pore (PTP), a key channel in cell death. Shrinking mitochondria inhibit PTP opening, offering new therapeutic targets.

Area of Science:

  • Mitochondrial physiology
  • Cell death mechanisms
  • Ion channel regulation

Background:

  • The permeability transition pore (PTP) is a critical mitochondrial inner membrane channel.
  • PTP opening is Ca(2+)-sensitive and implicated in various cell death pathways.
  • PTP regulation is influenced by matrix factors whose concentrations depend on mitochondrial volume.

Purpose of the Study:

  • To investigate the role of mitochondrial volume in regulating the permeability transition pore (PTP).
  • To understand how changes in mitochondrial volume affect PTP opening thresholds and sensitivity to regulatory factors.

Main Methods:

  • Rat liver mitochondria were incubated in media of varying osmolarity to induce changes in mitochondrial volume.
  • The Ca(2+) threshold for PTP opening was measured under different osmolarity conditions.
  • The influence of mitochondrial volume on PTP regulation was assessed in the presence and absence of key regulatory molecules like Mg(2+), adenine nucleotides, cyclosporin A (CsA), and ubiquinone 0 (Ub(0)).

Main Results:

  • Decreased mitochondrial volume significantly increased the Ca(2+) threshold required for PTP opening, indicating PTP inhibition.
  • This shrinkage-induced inhibition was independent of changes in protonmotive force, pyridine nucleotide redox state, or adenine nucleotide levels.
  • Mitochondrial volume changes modulated the efficacy of PTP regulators: Mg(2+) and Ub(0) became more inhibitory, while CsA became less inhibitory upon shrinkage.
  • The effect of mitochondrial volume on PTP regulation was dependent on Mg(2+) levels.

Conclusions:

  • Mitochondrial volume is a critical, previously unrecognized regulator of the permeability transition pore (PTP).
  • Mitochondrial shrinkage inhibits PTP opening by altering the pore's sensitivity to regulatory factors.
  • These findings suggest novel strategies for pharmacological modulation of the PTP by targeting mitochondrial volume.

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