The Mechanistic Function of the NOD-like Receptor NLRX1 in Apoptosis and Cell Death in the Nervous System

The mitochondrial protein NLRX1 belongs to the family of cytosolic nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs). NLRs respond to invasive pathogens, and danger signals released from dead or dying cells. The function of NLRX1 was previously reported to be in anti-viral immunity, however we propose a non-immune role for this protein in apoptosis. We show here the function of NLRX1 to be inhibitory to extrinsic apoptosis and permissive to intrinsic apoptosis. Furthermore, we validate the previously reported interaction between NLRX1 and sterile-α and TIR motif containing protein 1 (SARM1). SARM1 is expressed in the nervous system, and has a pro-apoptotic function in addition to its role in promoting Wallerian degeneration. We found NLRX1 to have both SARM1-dependent and -independent functions during apoptosis. Furthermore, we test NLRX1 function during Wallerian degeneration following axotomy, and a central nervous system injury model involving ischemic stroke.M.Sc.2017-12-02 00:00:0