The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy.

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.