TIR domains of plant immune receptors are NAD ⁺ -cleaving enzymes that promote cell death

TLDR

Plants trigger cell death during pathogen infection by depleting NAD+, a process mediated by TIR domains in nucleotide‑binding leucine‑rich repeat immune receptors, a mechanism also linked to NAD+ loss in mammalian Wallerian degeneration. The authors demonstrate that plant TIR domains cleave NAD+ to initiate cell‑death signaling in response to pathogens. These results are reported in Horsefield et al. and Wan et al., Science, this issue, pp.

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