The mitochondrial proteins NLRX1 and TUFM form a Complex that regulates type I interferon and Autophagy

Yu Lei, et al. Immunity 36: 933-946(June 2012)

Speaker: Kuan-Jung Lin (林冠蓉)                                Time:14:00~15:00, Oct.31, 2012

Commentator: Chiou-Feng Lin, Ph.D. (林秋烽老師)   Place: Room 601

Abstract

The Retinoic acid-inducible gene I (RIG-I)–like receptors (RLRs) of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferon (IFN) [1]. NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS to attenuates MAVS-RLR signaling [2]. The authors confirmed that NLRX1 attenuated IFN-I production but additionally promoted autophagy upon Vesicular stomatitis virus (VSV)infection. Autophagy is an important component and regulator of the host innate immunity against viral infections.However, the mechanism of how NLRX1 promote autophagy is little known. First, the authors employed high-throughput quantitative mass spectrometry and endogenous protein-protein interaction to reveal an NLRX1-interacting protein, mitochondrial Tu translation elongation factor (TUFM). TUFM associates with Atg5-Atg12 conjugate and Atg16L1 and promotes autophagy. Using NLRX^-/- cells, the authors found that increased IFN-I and decreased autophagy provide an advantage for host defense to against VSV. Together, this study demonstrates that NLRX1 dually regulated IFN-I and autophagy through the engagement of a mitochondrial protein, TUFM.

Reference

1. Brenner, D., and Mak, T.W. (2009). Mitochondrial cell death effectors. Curr. Opin. Cell Biol. 21, 871–877.

2. Allen, I.C et al (2011) NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-IMAVS and TRAF6-NF-kB signaling pathways. Immunity 34, 854–865.