Mito immunity

杨柳

CHEN/ELSEVIER
% m  D3 ^3 Q# W  Z1 N, |, O
7 `' c+ z, b# C& ~+ H6 Q1 PMitochondria may serve as a surveillance site where innate immune responses and apoptosis are coordinated, say Rashu Seth, Zhijian Chen, and colleagues (UTSW, Dallas, Texas). They base this idea on their discovery of an antiviral protein that hangs out on mitochondria.
- G. @0 j' x. Q7 S" E' ~" _8 ?& o2 M3 t( N
The protein was discovered by three groups and named MAVS, VISA, and IPS-1. Overexpression of MAVS (named for its mitochondrial antiviral signaling) induces interferon expression and thus increased antiviral defenses. It operates downstream of RIG-I, which detects viral double-stranded RNA, but upstream of the NF-B and IRF3 families of transcription factors. RNAi of MAVS abolishes viral activation of NF-B and IRF3 and thus knocks out the antiviral response.MAVS function requires its transmembrane domain, which resembles that of the antiapoptosis protein Bcl-2. Both proteins are found on mitochondria. This puts MAVS closer to some viruses, which replicate using membranes such as the ER and perhaps mitochondria. It may also allow the coordination of decisions by the innate immune system and the apoptosis machinery; some members of the latter have already been implicated in innate immunity. Chen suggests that innate immunity may be just one more service that mitochondria provide for the cell.
6 X. y$ o8 e5 T( N/ T4 @2 u5 \" {2 H3 }$ G0 ^& h
References:0 e" F. C5 {( j/ R( X3 U
: M! U: M1 A! j. @
Kawai, T., et al. 2005. Nat. Immunol. doi:10.1038/ni1243.3 r( e$ ?/ S- }" L" H3 x
4 _5 q7 W- r( l# |
Seth, R.B., et al. 2005. Cell. 122:669–682.
! o2 F' p; L* J+ r6 Y3 k/ b0 v; Y* \' x. U; d6 B" Q) B3 M
Xu, L.-G., et al. 2005. Mol. Cell. 19:727–740.(MAVS (green) works from mitochondria (re)