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.

Cell Research
|August 12, 2009
PubMed

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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