title: The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy.
abstract: The NLR (nucleotide-binding domain leucine-rich repeat containing) proteins serve as regulators of inflammatory signaling pathways. NLRX1, a mitochondria-localized NLR protein, has been previously shown to negatively regulate inflammatory cytokine production activated via the MAVS-DDX58 (RIG-I) pathway. The literature also indicates that DDX58 has a negative impact upon autophagy. Consistent with the inhibitory role of NLRX1 on DDX58, our recent study indicates a role of NLRX1 in augmenting virus-induced autophagy. This effect is through its interaction with another mitochondrial protein TUFM (Tu translation elongation factor, mitochondrial, also known as EF-TuMT, COXPD4, and P43). TUFM also reduces DDX58-activated cytokines but augments autophagy. Additionally it interacts with ATG12-ATG5-ATG16L1 to form a molecular complex that modulates autophagy. The work shows that both NLRX1 and TUFM work in concert to reduce cytokine response and augment autophagy.
authors: Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors: Yu
authors: Y
authors: Lei
authors: Haitao
authors: H
authors: Wen
authors: Jenny P Y
authors: JP
authors: Ting
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007370:Interferon Type I / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism*; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D024101:Mitochondrial Proteins; C527006:NLRX1 protein, human; D019913:Nuclear Localization Signals; D011971:Receptors, Immunologic; C091648:TUFM protein, human; C452820:RIGI protein, human; D010444:Peptide Elongation Factor Tu; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: ATG12; ATG16L1; ATG5; NLRX1; RIG-I; RLR; TUFM; autophagy; interferon