Fluofarma is glad to announce a new scientific publication in the journal Cell
Research:
Outer membrane VDAC1 controls permeability
transition of the inner mitochondrial membrane in cellulo during
stress-induced apoptosis
Flora Tomaselloa,b, Angela Messinab,c, Lydia Lartiguea, Laura Schembria, Chantal Medinaa, Simona Reinab,c, Didier Thoravald, Marc Crouzetd, François Ichasa,e, Vito De Pintob,c and Francesca De Giorgia,e
a INSERM U916, Institut Bergonié, 229 cours de
l'Argonne, 33076 Bordeaux, France
b Dipartimento Scienze Chimiche, Università
di Catania, Catania, Italia
c Istituto Nazionale di Biomembrane e
Biosistemi, Sezione di Catania, Roma, Italia
d CNRS UMR 5095, Université Bordeaux 2, 146
rue Leo Saignat, 33076 Bordeaux, France
e Fluofarma, 2 rue Robert Escarpit, 33600
Pessac, 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-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.
Cell Research advance online publication 11 August 2009; doi:
10.1038/cr.2009.98