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Cited by 450

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore

Open access
Jacotot, Etienne, Ravagnan, Luigi, Loeffler, Markus, Ferri, Karine F., Vieira, Helena L.A., Zamzami, Naoufal, Costantini, Paola, Druillennec, Sabine, Hoebeke, Johan, Briand, Jean Paul, Irinopoulou, Theano, Daugas, Eric, Susin, Santos A., Cointe, Denis, Xie, Zhi Hua, Reed, John C., Roques, Bernard P., Kroemer, Guido·2000·The Journal of Experimental Medicine

Abstract

Viral protein R (Vpr) encoded by HIV-1 is a facultative inducer of apoptosis. When added to intact cells or purified mitochondria, micromolar and submicromolar doses of synthetic Vpr cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨm), as well as the mitochondrial release of apoptogenic proteins such as cytochrome c or apoptosis inducing factor. The same structural motifs relevant for cell killing are responsible for the mitochondriotoxic effects of Vpr. Both mitochondrial and cytotoxic Vpr effects are prevented by Bcl-2, an inhibitor of the permeability transition pore complex (PTPC). Coincubation of purified organelles revealed that nuclear apoptosis is only induced by Vpr when mitochondria are present yet can be abolished by PTPC inhibitors. Vpr favors the permeabilization of artificial membranes containing the purified PTPC or defined PTPC components such as the adenine nucleotide translocator (ANT) combined with Bax. Again, this effect is prevented by addition of recombinant Bcl-2. The Vpr COOH terminus binds purified ANT, as well as a molecular complex containing ANT and the voltage-dependent anion channel (VDAC), another PTPC component. Yeast strains lacking ANT or VDAC are less susceptible to Vpr-induced killing than control cells yet recover Vpr sensitivity when retransfected with yeast ANT or human VDAC. Hence, Vpr induces apoptosis via a direct effect on the mitochondrial PTPC.

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Crossref · 10.1084/jem.191.1.33

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Metadata

Authors
Jacotot, E., Ravagnan, L., Loeffler, M., Ferri, K. F., Vieira, H. L. A., Zamzami, N., Costantini, P., Druillennec, S., Hoebeke, J., Briand, J. P., Irinopoulou, T., Daugas, E., Susin, S. A., Cointe, D., Xie, Z. H., Reed, J. C., Roques, B. P., & Kroemer, G.
Venue
The Journal of Experimental Medicine
Published
2000-01-03
Volume
191
Issue
1
Pages
33-46
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2171662092
Cited by
450
References
2
FWCI
13.18
Type
journal article
Language
en
Open access
bronze

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