The myxoma poxvirus protein, M11L, prevents apoptosis by direct interaction with the mitochondrial permeability transition pore

被引:93
作者
Everett, H
Barry, M
Sun, XJ
Lee, SF
Frantz, C
Berthiaume, LG
McFadden, G [1 ]
Bleackley, RC
机构
[1] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6G 2V4, Canada
[2] John P Robarts Res Inst, London, ON N6G 2V4, Canada
[3] Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada
[4] Univ Alberta Hosp, Dept Lab Med & Pathol, Edmonton, AB T6G 2B7, Canada
[5] Univ Alberta, Cross Canc Inst, Dept Expt Oncol, Edmonton, AB T6G 1Z2, Canada
[6] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2S2, Canada
[7] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada
关键词
apoptosis; mitochondria; PK11195; protoporphyrin IX; Poxviridae;
D O I
10.1084/jem.20011247
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
M11L, an antiapoptotic protein essential for the virulence of the myxoma poxvirus, is targeted to mitochondria and prevents the loss of mitochondrial membrane potential that accompanies cell death. In this study we show, using a cross-linking approach, that M11L physically associates with the mitochondrial peripheral benzodiazepine receptor (PBR) component of the permeability transition (PT) pore. Close association of M11L and the PBR is also indicated by fluorescence resonance energy transfer (FRET) analysis. Stable expression of M11L prevents the release of mitochondrial cytochrome c induced by staurosporine or protoporphyrin IX (PPIX), a ligand of the PBR. Transiently expressed M11L also prevents mitochondrial membrane potential loss induced by PPIX, or induced by staurosporine in combination with PK11195, another ligand of the PBR,. Myxoma virus infection and the associated expression of early proteins, including M11L, protects cells from staurosporine- and Fas-mediated mitochondrial membrane potential loss and this effect is augmented by the presence of PBR. We conclude that M11L regulates the mitochondrial permeability transition pore complex, most likely by direct modulation of the PBR.
引用
收藏
页码:1127 / 1139
页数:13
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