The mitochondrial antiviral signaling protein, MAVS, is cleaved during apoptosis.
Apoptosis of virus-infected cells is one important host strategy used to limit viral infection. Recently a member of the innate immune signaling pathway, MAVS, was localized to mitochondria, an organelle important for apoptosis regulation. Here we investigate what role MAVS may play in apoptosis. Induction of cell death led to the rapid cleavage of MAVS, resulting in its release from the outer mitochondrial membrane. This cleavage is blocked in cells incubated with proteasome or caspase inhibitors. Transfection of synthetic viral dsRNA and dsDNA also led to cleavage of MAVS, indicating that this process may be important during infection. Preventing apoptosis by over-expression of anti-apoptotic Bcl-xL blocks MAVS cleavage, placing this process downstream of caspase activation in the apoptotic program.
Scott
Iain
I
Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2C-1014, Building 35, 9000 Rockville Pike, Bethesda, MD 20892, USA. scotti@ninds.nih.gov
Norris
Kristi L
KL
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004266:DNA Virus Infections / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012327:RNA Virus Infections / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D051020:bcl-X Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004279:DNA, Viral; C505371:MAVS protein, human; D024101:Mitochondrial Proteins; D012367:RNA, Viral; D051020:bcl-X Protein; D020169:Caspases; D046988:Proteasome Endopeptidase Complex