Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation

Emy Basso, Valeria Petronilli, Michael Forte, Paolo Bernardi

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Energized mouse liver mitochondria displayed the same calcium retention capacity (a sensitive measure of the propensity of the permeability transition pore (PTP) to open) irrespective of whether phosphate, arsenate, or vanadate was the permeating anion. Unexpectedly, however, phosphate was specifically required for PTP desensitization by cyclosporin A (CsA) or by genetic inactivation of cyclophilin D (CyP-D). Indeed, when phosphate was replaced by arsenate, vanadate, or bicarbonate, the inhibitory effects of CsA and of CyP-D ablation on the PTP disappeared. After loading with the same amount of Ca 2+ in the presence of arsenate or vanadate but in the absence of phosphate, the sensitivity of the PTP to a variety of inducers was identical in mitochondria from wild-type mice, CyP-D-null mice, and wild-type mice treated with CsA. These findings call for a reassessment of conclusions on the role of the PTP in cell death that are based on the effects of CsA or of CyP-D ablation.

Original languageEnglish (US)
Pages (from-to)26307-26311
Number of pages5
JournalJournal of Biological Chemistry
Volume283
Issue number39
DOIs
StatePublished - Sep 26 2008

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Ablation
Cyclosporine
Vanadates
Permeability
Phosphates
Mitochondria
Cell death
Bicarbonates
Liver
Liver Mitochondrion
Anions
Calcium
Cell Death
mitochondrial permeability transition pore
cyclophilin D
arsenic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation. / Basso, Emy; Petronilli, Valeria; Forte, Michael; Bernardi, Paolo.

In: Journal of Biological Chemistry, Vol. 283, No. 39, 26.09.2008, p. 26307-26311.

Research output: Contribution to journalArticle

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