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Titolo:
Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein R and Bcl-2
Autore:
Jacotot, E; Ferri, KF; El Hamel, C; Brenner, C; Druillennec, S; Hoebeke, J; Rustin, P; Metivier, D; Lenoir, C; Geuskens, M; Vieira, HLA; Loeffler, M; Belzacq, AS; Briand, JP; Zamzami, N; Edelman, L; Xie, ZH; Reed, JC; Roques, BP; Kroemer, G;
Indirizzi:
Inst Gustave Roussy, CNRS, UMR 1599, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Univ Paris 05, CNRS, UMR 860, INSERM,U266,Unite Pharmacochim Mol & Struct,F-75006 Paris, France Univ Paris 05 Paris France F-75006 im Mol & Struct,F-75006 Paris, France Univ Technol Compiegne, CNRS, UMR A6022, F-60205 Compiegne, France Univ Technol Compiegne Compiegne France F-60205 -60205 Compiegne, France CNRS, UPR 9021, Inst Biol Mol & Cellulaire Immunol & Chim Therape, F-67084Strasbourg, France CNRS Strasbourg France F-67084 & Chim Therape, F-67084Strasbourg, France Hop Necker Enfants Malad, INSERM, U393, Unite Rech Handicaps Genet Enfant,F-75015 Paris, France Hop Necker Enfants Malad Paris France F-75015 fant,F-75015 Paris, France Free Univ Brussels, B-1640 Rhode St Genese, Belgium Free Univ Brussels Rhode St Genese Belgium B-1640 ode St Genese, Belgium Inst Pasteur, Lab Technol Cellulaire, F-75015 Paris, France Inst Pasteur Paris France F-75015 hnol Cellulaire, F-75015 Paris, France Burnham Inst, La Jolla, CA 92037 USA Burnham Inst La Jolla CA USA 92037Burnham Inst, La Jolla, CA 92037 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 4, volume: 193, anno: 2001,
pagine: 509 - 519
SICI:
0022-1007(20010219)193:4<509:COMMPB>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; C-TERMINAL DOMAIN; DEPENDENT ANION CHANNEL; TRANSITION PORE; CELL-DEATH; FAMILY PROTEINS; CYTOCHROME-C; INHIBITS APOPTOSIS; ADP/ATP CARRIER; OUTER-MEMBRANE;
Keywords:
ADP/ATP translocase; HIV; Vpr; mitochondria; Bcl-2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Kroemer, G Inst Gustave Roussy, CNRS, UMR 1599, Pavillon Rech 1,39 Rue Camille Desmoulins, F-94805 Villejuif, France Inst Gustave Roussy Pavillon Rech 1,39 Rue Camille Desmoulins Villejuif France F-94805
Citazione:
E. Jacotot et al., "Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein R and Bcl-2", J EXP MED, 193(4), 2001, pp. 509-519

Abstract

Viral protein R (Vpr), an apoptogenic accessory protein encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore complex, which comprises the voltage-dependent anion channel (VDAC) in the outer membrane (OM) and the adenine nucleotide translocator (ANT) in the inner membrane. Here, we demonstrate that a synthetic Vpr-derived peptide (Vpr52-96) specifically binds to the intermembrane face of the ANT with an affinity in the nanomolar range. Taking advantage of this specific interaction, we determined the role of ANTin the control of MMP. In planar lipid bilayers, Vpr52-96 and purified ANTcooperatively form large conductance channels. This cooperative channel formation relies on a direct protein-protein interaction since it is abolished by the addition of a peptide corresponding to the Vpr binding site of ANT. When added to isolated mitochondria, Vpr52-96 uncouples the respiratory chain and induces a rapid inner MMP to protons and NADH. This inner MMP precedes outer MMP to cytochrome c. Vpr52-96-induced matrix swelling and inner MMP both are prevented by preincubation of purified mitochondria with recombinant Bcl-2 protein. In contrast to Konig's polyanion (PA10), a specific inhibitor of the VDAC, Bcl-2 fails to prevent Vpr52-96 from crossing the mitochondrial OM. Rather, Bcl-2 reduces the ANT-Vpr interaction, as determinedby affinity purification and plasmon resonance studies. Concomitantly, Bcl-2 suppresses channel formation by the ANT-Vpr complex in synthetic membranes. In conclusion, both Vpr and Bcl-2 modulate MMP through a direct interaction with ANT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 06:36:07