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: Yu Lei, Haitao Wen, Jenny P Y Ting
• Journal: Autophagy (Autophagy) Vol. 9 Issue 3 Pg. 432-3 (Mar 2013) ISSN: 1554-8635 [Electronic] United States
• PMID: 23321557 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interferon Type I
• Mitochondrial Proteins
• NLRX1 protein, human
• Nuclear Localization Signals
• Receptors, Immunologic
• TUFM protein, human
• DDX58 protein, human
• Peptide Elongation Factor Tu
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• Animals
• Apoptosis
• Autophagy
• Cytokines (metabolism)
• DEAD Box Protein 58
• DEAD-box RNA Helicases (metabolism)
• Fibroblasts (metabolism)
• Gene Expression Regulation
• Humans
• Inflammation
• Interferon Type I (metabolism)
• Mice
• Mitochondria (metabolism)
• Mitochondrial Proteins (metabolism)
• Nuclear Localization Signals (metabolism)
• Peptide Elongation Factor Tu (metabolism)
• Receptors, Immunologic
• Signal Transduction