The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 4 November 2002. doi:10.1084/jem.20011247
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Everett, H.
Right arrow Articles by Bleackley, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Everett, H.
Right arrow Articles by Bleackley, R. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2002/11/1127 $5.00
The Journal of Experimental Medicine, Volume 196, Number 9, 1127-1140

The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore

Helen Everett1, Michele Barry2, Xuejun Sun3, Siow Fong Lee4, Christine Frantz1, Luc G. Berthiaume5, Grant McFadden6 and R. Chris Bleackley1

1 Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G2H7, Canada
2 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G2S2, Canada
3 Department of Experimental Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta T6G1Z2, Canada
4 Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta T6G2B7, Canada
5 Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G2H7, Canada
6 Department of Microbiology and Immunology, University of Western Ontario and The John P. Robarts Research Institute, London, Ontario N6G2V4, Canada

Address correspondence to Dr. Grant McFadden, Department of Microbiology and Immunology, University of Western Ontario and The John P. Robarts Research Institute, London, Ontario N6G2V4, Canada. Phone: 519-663-3184; Fax: 519-663-3847; E-mail: mcfadden{at}robarts.ca

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.

Key Words: apoptosis • mitochondria • PK11195 • protoporphyrin IX • Poxviridae


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS