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Updated: Jun 21, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during
Flora Tomasello1, Angela Messina, Lydia Lartigue
1INSERM U916, Université Bordeaux 2, Institut Bergonié, 33076 Bordeaux, France.
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.
Insights
Voltage-dependent anion channel 1 (VDAC1) triggers mitochondrial permeability transition (MPT) and apoptosis. Silencing VDAC1 inhibits MPT, revealing its crucial role in oxidative stress-induced cell death.
Area of Science:
- Mitochondrial biology
- Cell death pathways
- Ion channel function
Background:
- Voltage-dependent anion channel 1 (VDAC1) is a key component of the mitochondrial outer membrane.
- VDAC1 is implicated in the permeability transition pore (PTP) complex and mitochondrial permeability transition (MPT).
Purpose of the Study:
- To investigate the role of VDAC1 in MPT and its contribution to oxidative stress-induced apoptosis at the single live cell level.
Main Methods:
- Single live cell imaging
- VDAC1 overexpression and silencing
- Assessment of mitochondrial inner membrane potential
- Involvement of Cyclosporin A, Cyclophilin D, Bcl-2, and Bcl-X(L)
Main Results:
- VDAC1 overexpression induced MPT at the mitochondrial inner membrane.
- VDAC1 silencing inhibited selenite-induced MPT.
- VDAC1-dependent MPT involved a positive feedback loop with reactive oxygen species and p38-MAPK.
- This process led to canonical apoptosis, including cytochrome c release and caspase 3 activation.
Conclusions:
- VDAC1 is a critical component of the PTP complex, localized at the mitochondrial outer membrane.
- VDAC1-dependent MPT acts upstream in oxidative stress-induced apoptosis.
- VDAC1 plays a causal role in the apoptotic response to oxidative stress.
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