NAD ⁺ cleavage activity by animal and plant TIR domains in cell death pathways

TLDR

Plants trigger a hypersensitive response by sacrificing infected cells, mediated by NLRs with TIR domains, and recent studies show TIR domains cleave NAD+ to drive cell‑death signaling, a mechanism also linked to mammalian TIR proteins in Wallerian degeneration. The studies demonstrate that TIR domains cleave NAD+ to activate pathogen‑induced cell‑death signaling. Published in Science, pages 793–799.

Abstract

NAD depletion as pathogen response One way that plants respond to pathogen infection is by sacrificing the infected cells. The nucleotide-binding leucine-rich repeat immune receptors responsible for this hypersensitive response carry Toll/interleukin-1 receptor (TIR) domains. In two papers, Horsefield et al. and Wan et al. report that these TIR domains cleave the metabolic cofactor nicotinamide adenine dinucleotide (NAD + ) as part of their cell-death signaling in response to pathogens. Similar signaling links mammalian TIR-containing proteins to NAD + depletion during Wallerian degeneration of neurons. Science , this issue p. 793 , p. 799