Cited by 161Mitochondrial Function and PathologyCell death mechanisms and regulationCardiac Ischemia and Reperfusion

Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during stress-induced apoptosis

Tomasello, Flora, Messina, Angela, Lartigue, Lydia, Schembri, Laura, Medina, Chantal, Reina, Simona, Thoraval, Didier, Crouzet, Marc +3 more·2009·Cell Research

Abstract

Voltage-dependent anion channel (VDAC)1 is the main channel of the mitochondrial outer membrane (MOM) and it has been proposed to be part of the permeability transition pore (PTP), a putative multiprotein complex candidate agent of the mitochondrial permeability transition (MPT). Working at the single live cell level, we found that overexpression of VDAC1 triggers MPT at the mitochondrial inner membrane (MIM). Conversely, silencing VDAC1 expression results in the inhibition of MPT caused by selenite-induced oxidative stress. This MOM-MIM crosstalk was modulated by Cyclosporin A and mitochondrial Cyclophilin D, but not by Bcl-2 and Bcl-X(L), indicative of PTP operation. VDAC1-dependent MPT engages a positive feedback loop involving reactive oxygen species and p38-MAPK, and secondarily triggers a canonical apoptotic response including Bax activation, cytochrome c release and caspase 3 activation. Our data thus support a model of the PTP complex involving VDAC1 at the MOM, and indicate that VDAC1-dependent MPT is an upstream mechanism playing a causal role in oxidative stress-induced apoptosis.

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Crossref · 10.1038/cr.2009.98

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Authors
Tomasello, F., Messina, A., Lartigue, L., Schembri, L., Medina, C., Reina, S., Thoraval, D., Crouzet, M., Ichas, F., De Pinto, V., & De Giorgi, F.
Affiliations
  • University of Catania (IT)
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
Venue
Cell Research
Published
2009-08-11
Volume
19
Issue
12
Pages
1363-1376
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
OpenAlex
W2054828537
Cited by
161
References
71
Citations by year
2026: 11 · 2025: 13 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 13 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 11 · 2015: 11 · 2014: 14 · 2013: 8 · 2012: 8
FWCI
4.02
Type
journal article
Language
en
Open access
closed
Locations
  • Cell Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Ligue Contre le Cancer
  • Università di Catania
  • Institut Bergonié
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
VDAC1, mitochondrial permeability transition, mitochondrial permeability transition pore, mitochondrial outer membrane, inner mitochondrial membrane, oxidative stress-induced apoptosis, selenite, cyclosporine, cyclophilin D, reactive oxygen species, p38 MAPK, Bax activation, cytochrome c release, caspase-3
MeSH terms
Peptidyl-Prolyl Isomerase F, Animals, Cell Membrane Permeability, Chlorocebus aethiops, HeLa Cells, Humans, Stress, Physiological, Cyclosporine, Sodium Selenite, Oxidative Stress, COS Cells, Gene Silencing, Cyclophilins, Feedback, Physiological, Voltage-Dependent Anion Channel 1, Apoptosis Regulatory Proteins, Mitochondrial Membranes, Membrane Potential, Mitochondrial

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