PMID- 10620603
OWN - NLM
STAT- MEDLINE
DCOM- 20000207
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 191
IP  - 1
DP  - 2000 Jan 3
TI  - The HIV-1 viral protein R induces apoptosis via a direct effect on the
      mitochondrial permeability transition pore.
PG  - 33-46
AB  - 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 (DeltaPsi(m)), 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.
FAU - Jacotot, E
AU  - Jacotot E
AD  - Centre National de la Recherche Scientifique, F-94801 Villejuif, France.
FAU - Ravagnan, L
AU  - Ravagnan L
FAU - Loeffler, M
AU  - Loeffler M
FAU - Ferri, K F
AU  - Ferri KF
FAU - Vieira, H L
AU  - Vieira HL
FAU - Zamzami, N
AU  - Zamzami N
FAU - Costantini, P
AU  - Costantini P
FAU - Druillennec, S
AU  - Druillennec S
FAU - Hoebeke, J
AU  - Hoebeke J
FAU - Briand, J P
AU  - Briand JP
FAU - Irinopoulou, T
AU  - Irinopoulou T
FAU - Daugas, E
AU  - Daugas E
FAU - Susin, S A
AU  - Susin SA
FAU - Cointe, D
AU  - Cointe D
FAU - Xie, Z H
AU  - Xie ZH
FAU - Reed, J C
AU  - Reed JC
FAU - Roques, B P
AU  - Roques BP
FAU - Kroemer, G
AU  - Kroemer G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Gene Products, vpr)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (vpr Gene Products, Human Immunodeficiency Virus)
SB  - IM
SB  - X
MH  - *Apoptosis
MH  - Cell-Free System
MH  - Gene Products, vpr/chemistry/*physiology
MH  - HIV-1/*physiology
MH  - Humans
MH  - Jurkat Cells
MH  - Mitochondria/*physiology
MH  - Permeability
MH  - Proto-Oncogene Proteins c-bcl-2/physiology
MH  - vpr Gene Products, Human Immunodeficiency Virus
PMC - PMC2195797
EDAT- 2000/01/06 00:00
MHDA- 2000/01/06 00:01
CRDT- 2000/01/06 00:00
PHST- 2000/01/06 00:00 [pubmed]
PHST- 2000/01/06 00:01 [medline]
PHST- 2000/01/06 00:00 [entrez]
AID - 10.1084/jem.191.1.33 [doi]
PST - ppublish
SO  - J Exp Med. 2000 Jan 3;191(1):33-46. doi: 10.1084/jem.191.1.33.