title: The mitochondrial proteins NLRX1 and TUFM form a complex that regulates type I interferon and autophagy.
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.
authors: The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Yu
authors: Y
authors: Lei
authors: Haitao
authors: H
authors: Wen
authors: Yanbao
authors: Y
authors: Yu
authors: Debra J
authors: DJ
authors: Taxman
authors: Lu
authors: L
authors: Zhang
authors: Douglas G
authors: DG
authors: Widman
authors: Karen V
authors: KV
authors: Swanson
authors: Kwun-Wah
authors: KW
authors: Wen
authors: Blossom
authors: B
authors: Damania
authors: Chris B
authors: CB
authors: Moore
authors: Patrick M
authors: PM
authors: Giguère
authors: David P
authors: DP
authors: Siderovski
authors: John
authors: J
authors: Hiscott
authors: Babak
authors: B
authors: Razani
authors: Clay F
authors: CF
authors: Semenkovich
authors: Xian
authors: X
authors: Chen
authors: Jenny P-Y
authors: JP
authors: Ting
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000502:physiology; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000502:physiology; D010444:Peptide Elongation Factor Tu / Q000737:chemistry / Q000502:physiology*; D025941:Protein Interaction Mapping; D011506:Proteins / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013047:Specific Pathogen-Free Organisms; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491971:Atg12 protein, mouse; C532820:Atg16l1 protein, mouse; C495773:Atg5 protein, mouse; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D016207:Cytokines; D007370:Interferon Type I; C505371:MAVS protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; C527006:NLRX1 protein, human; C555655:NLRX1 protein, mouse; D011506:Proteins; D011993:Recombinant Fusion Proteins; C091648:TUFM protein, human; C503356:Ddx58 protein, mouse; D010444:Peptide Elongation Factor Tu; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases