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

被引：0
作者：
Flora Tomasello
Angela Messina
Lydia Lartigue
Laura Schembri
Chantal Medina
Simona Reina
Didier Thoraval
Marc Crouzet
François Ichas
Vito De Pinto
Francesca De Giorgi
机构：
[1] INSERM U916,Dipartimento Scienze Chimiche
[2] Université Bordeaux 2,undefined
[3] Institut Bergonié,undefined
[4] Università di Catania,undefined
[5] Istituto Nazionale di Biomembrane e Biosistemi,undefined
[6] CNRS UMR 5095,undefined
[7] Université Bordeaux 2,undefined
[8] FluoFarma,undefined
来源：
Cell Research | 2009年 / 19卷
关键词：
apoptosis; mitochondria; VDAC; MPT; PTP; oxidative stress; selenite;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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-XL, 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.
引用
收藏
页码：1363 / 1376
页数：13
相关论文
共 190 条
  • [41] Galluzzi L(2000) release Nat Cell Biol 2 156-162
  • [42] Brenner C(2001)The mitochondrial permeability transition as a target for neuroprotection Mol Biol Cell 12 2482-2496
  • [43] Shi Y(2004)Reactive oxygen species (ros)-induced ros release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes Cancer Res 64 85-93
  • [44] Chen J(2003)Selenite activates caspase-independent necrotic cell death in Jurkat T cells and J774.2 macrophages by affecting mitochondrial oxidant generation J Cell Biol 160 65-75
  • [45] Weng C(1997)The coordinate release of cytochrome J Biol Chem 272 12116-12121
  • [46] Brdiczka DG(1997) during apoptosis is rapid, complete and kinetically invariant Biomed Environ Sci 10 333-339
  • [47] Zorov DB(1994)Targeting of a tail-anchored protein to endoplasmic reticulum and mitochondrial outer membrane by independent but competing pathways Free Radic Biol Med 17 45-64
  • [48] Sheu S(2002)Cyclophilin D, a component of the permeability transition-pore, is an apoptosis repressor Biochimie 84 153-166
  • [49] Fiek C(2004)Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis Science 303 1010-1014
  • [50] Benz R(2004)Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site Cell 117 773-786
12345678910