Properties of the permeability transition in VDAC1-/- mitochondria

Alexandra Krauskopf, Ove Eriksson, William J. Craigen, Michael A. Forte, Paolo Bernardi

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

Abstract

Opening of the permeability transition pore (PTP), a high-conductance mitochondrial channel, causes mitochondrial dysfunction with Ca2+ deregulation, ATP depletion, release of pyridine nucleotides and of mitochondrial apoptogenic proteins. Despite major efforts, the molecular nature of the PTP remains elusive. A compound library screening led to the identification of a novel high affinity PTP inhibitor (Ro 68-3400), which labeled a ∼32 kDa protein that was identified as isoform 1 of the voltage-dependent anion channel (VDAC1) [A.M. Cesura, E. Pinard, R. Schubenel, V. Goetschy, A. Friedlein, H. Langen, P. Polcic, M.A. Forte, P. Bernardi, J.A. Kemp, The voltage-dependent anion channel is the target for a new class of inhibitors of the mitochondrial permeability transition pore. J. Biol. Chem. 278 (2003) 49812-49818]. In order to assess the role of VDAC1 in PTP formation and activity, we have studied the properties of mitochondria from VDAC1-/- mice. The basic properties of the PTP in VDAC1-/- mitochondria were indistinguishable from those of strain-matched mitochondria from wild-type CD1 mice, including inhibition by Ro 68-3400, which labeled identical proteins of 32 kDa in both wild-type and VDAC1-/- mitochondria. The labeled protein could be separated from all VDAC isoforms. While these results do not allow to exclude that VDAC is part of the PTP, they suggest that VDAC is not the target for PTP inhibition by Ro 68-3400.

Original languageEnglish (US)
Pages (from-to)590-595
Number of pages6
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1757
Issue number5-6
DOIs
StatePublished - May 2006

Keywords

  • Mitochondria
  • Permeability transition
  • VDAC1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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