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Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D

Emy Basso1, Lisa Fante, Jonathan Fowlkes

  • 1Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Padova, Viale Giuseppe Colombo 3, I-35121 Padova, Italy.

The Journal of Biological Chemistry
|March 29, 2005
PubMed

Insights

Mitochondrial permeability transition pore (PTP) opening is less sensitive to calcium in mice lacking Cyclophilin D (CyP-D). CyP-D is the target for Cyclosporin A inhibition of PTP.

Area of Science:

  • Mitochondrial physiology
  • Cellular biology
  • Biochemistry

Background:

  • The mitochondrial permeability transition pore (PTP) plays a critical role in cell death.
  • Cyclophilin D (CyP-D) is a key regulator of PTP opening.
  • Understanding PTP regulation is crucial for therapeutic interventions.

Purpose of the Study:

  • To investigate the role of CyP-D in PTP properties using gene knockout mice.
  • To determine the specific modulatory effects of CyP-D on PTP sensitivity to calcium and other factors.
  • To elucidate the mechanism of PTP inhibition by Cyclosporin A (CsA).

Main Methods:

  • Mitochondria isolated from wild-type and Ppif-/- mice (lacking CyP-D).
  • Assessment of PTP opening triggered by calcium and other stimuli.
  • Evaluation of CsA effects on calcium retention capacity.

Main Results:

  • Mitochondria lacking CyP-D showed significantly reduced sensitivity to calcium-induced PTP opening.
  • CyP-D absence rendered the PTP insensitive to CsA inhibition.
  • PTP regulation by ubiquinone, depolarization, pH, adenine nucleotides, and thiol oxidants was unaffected by CyP-D absence.

Conclusions:

  • The PTP can form and open independently of CyP-D.
  • CyP-D is the primary target for CsA-mediated PTP inhibition.
  • CyP-D modulates PTP calcium sensitivity but not its response to other regulatory factors.

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