The Mitochondrial Proteins NLRX1 and TUFM Form a Complex that Regulates Type I Interferon and Autophagy

Yu Lei, Haitao Wen, Yanbao Yu, Debra J. Taxman, Lu Zhang, Douglas G. Widman, Karen V. Swanson, Kwun Wah Wen, Blossom Damania, Chris B. Moore, Patrick M. Giguère, David P. Siderovski, John Hiscott, Babak Razani, Clay F. Semenkovich, Xian Chen, Jenny P.Y. Ting

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalImmunity
Volume36
Issue number6
DOIs
StatePublished - Jun 29 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Lei, Y., Wen, H., Yu, Y., Taxman, D. J., Zhang, L., Widman, D. G., Swanson, K. V., Wen, K. W., Damania, B., Moore, C. B., Giguère, P. M., Siderovski, D. P., Hiscott, J., Razani, B., Semenkovich, C. F., Chen, X., & Ting, J. P. Y. (2012). The Mitochondrial Proteins NLRX1 and TUFM Form a Complex that Regulates Type I Interferon and Autophagy. Immunity, 36(6), 933-946. https://doi.org/10.1016/j.immuni.2012.03.025