Properties of the permeability transition in VDAC1-/- mitochondria

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

Research output: Contribution to journalArticle

163 Citations (Scopus)

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

Fingerprint

Mitochondria
Permeability
Voltage-Dependent Anion Channel 1
Protein Isoforms
Proteins
Voltage-Dependent Anion Channels
Deregulation
Screening
Nucleotides
Adenosine Triphosphate
Mitochondrial Proteins
Ro 68-3400

Keywords

  • Mitochondria
  • Permeability transition
  • VDAC1

ASJC Scopus subject areas

  • Biophysics

Cite this

Properties of the permeability transition in VDAC1-/- mitochondria. / Krauskopf, Alexandra; Eriksson, Ove; Craigen, William J.; Forte, Michael; Bernardi, Paolo.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1757, No. 5-6, 05.2006, p. 590-595.

Research output: Contribution to journalArticle

Krauskopf, Alexandra ; Eriksson, Ove ; Craigen, William J. ; Forte, Michael ; Bernardi, Paolo. / Properties of the permeability transition in VDAC1-/- mitochondria. In: Biochimica et Biophysica Acta - Bioenergetics. 2006 ; Vol. 1757, No. 5-6. pp. 590-595.
@article{8f58db567f2e4af3933e50b9bf8ab2c2,
title = "Properties of the permeability transition in VDAC1-/- mitochondria",
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.",
keywords = "Mitochondria, Permeability transition, VDAC1",
author = "Alexandra Krauskopf and Ove Eriksson and Craigen, {William J.} and Michael Forte and Paolo Bernardi",
year = "2006",
month = "5",
doi = "10.1016/j.bbabio.2006.02.007",
language = "English (US)",
volume = "1757",
pages = "590--595",
journal = "Biochimica et Biophysica Acta - Bioenergetics",
issn = "0005-2728",
publisher = "Elsevier",
number = "5-6",

}

TY - JOUR

T1 - Properties of the permeability transition in VDAC1-/- mitochondria

AU - Krauskopf, Alexandra

AU - Eriksson, Ove

AU - Craigen, William J.

AU - Forte, Michael

AU - Bernardi, Paolo

PY - 2006/5

Y1 - 2006/5

N2 - 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.

AB - 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.

KW - Mitochondria

KW - Permeability transition

KW - VDAC1

UR - http://www.scopus.com/inward/record.url?scp=33745618955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745618955&partnerID=8YFLogxK

U2 - 10.1016/j.bbabio.2006.02.007

DO - 10.1016/j.bbabio.2006.02.007

M3 - Article

C2 - 16626625

AN - SCOPUS:33745618955

VL - 1757

SP - 590

EP - 595

JO - Biochimica et Biophysica Acta - Bioenergetics

JF - Biochimica et Biophysica Acta - Bioenergetics

SN - 0005-2728

IS - 5-6

ER -