TY - JOUR
T1 - The Mitochondrial Proteins NLRX1 and TUFM Form a Complex that Regulates Type I Interferon and Autophagy
AU - Lei, Yu
AU - Wen, Haitao
AU - Yu, Yanbao
AU - Taxman, Debra J.
AU - Zhang, Lu
AU - Widman, Douglas G.
AU - Swanson, Karen V.
AU - Wen, Kwun Wah
AU - Damania, Blossom
AU - Moore, Chris B.
AU - Giguère, Patrick M.
AU - Siderovski, David P.
AU - Hiscott, John
AU - Razani, Babak
AU - Semenkovich, Clay F.
AU - Chen, Xian
AU - Ting, Jenny P.Y.
PY - 2012/6/29
Y1 - 2012/6/29
N2 - The mitochondrial protein MAVS (also known as IPS-1, VISA, and CARDIF) interacts with RIG-I-like receptors (RLRs) to induce type I interferon (IFN-I). NLRX1 is a mitochondrial nucleotide-binding, leucine-rich repeats (NLR)-containing protein that attenuates MAVS-RLR signaling. Using Nlrx1-/- cells, we confirmed that NLRX1 attenuated IFN-I production, but additionally promoted autophagy during viral infection. This dual function of NLRX1 paralleled the previously described functions of the autophagy-related proteins Atg5-Atg12, but NLRX1 did not associate with Atg5-Atg12. High-throughput quantitative mass spectrometry and endogenous protein-protein interaction revealed an NLRX1-interacting partner, mitochondrial Tu translation elongation factor (TUFM). TUFM interacted with Atg5-Atg12 and Atg16L1 and has similar functions as NLRX1 by inhibiting RLR-induced IFN-I but promoting autophagy. In the absence of NLRX1, increased IFN-I and decreased autophagy provide an advantage for host defense against vesicular stomatitis virus. This study establishes a link between an NLR protein and the viral-induced autophagic machinery via an intermediary partner, TUFM.
AB - The mitochondrial protein MAVS (also known as IPS-1, VISA, and CARDIF) interacts with RIG-I-like receptors (RLRs) to induce type I interferon (IFN-I). NLRX1 is a mitochondrial nucleotide-binding, leucine-rich repeats (NLR)-containing protein that attenuates MAVS-RLR signaling. Using Nlrx1-/- cells, we confirmed that NLRX1 attenuated IFN-I production, but additionally promoted autophagy during viral infection. This dual function of NLRX1 paralleled the previously described functions of the autophagy-related proteins Atg5-Atg12, but NLRX1 did not associate with Atg5-Atg12. High-throughput quantitative mass spectrometry and endogenous protein-protein interaction revealed an NLRX1-interacting partner, mitochondrial Tu translation elongation factor (TUFM). TUFM interacted with Atg5-Atg12 and Atg16L1 and has similar functions as NLRX1 by inhibiting RLR-induced IFN-I but promoting autophagy. In the absence of NLRX1, increased IFN-I and decreased autophagy provide an advantage for host defense against vesicular stomatitis virus. This study establishes a link between an NLR protein and the viral-induced autophagic machinery via an intermediary partner, TUFM.
UR - http://www.scopus.com/inward/record.url?scp=84863005844&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.03.025
DO - 10.1016/j.immuni.2012.03.025
M3 - Article
C2 - 22749352
AN - SCOPUS:84863005844
SN - 1074-7613
VL - 36
SP - 933
EP - 946
JO - Immunity
JF - Immunity
IS - 6
ER -