Figure 2. SARM1 structure and function.
A. The autoinhibitory SARM1 N terminus contains a mitochondria localization signal and ARM domains. The two SAM domains mediate multimerization. The C terminal TIR domain possesses intrinsic NAD+ cleavage activity.
B. SARM1 forms multimers. The TIR domains are inhibited in normal conditions, possibly through direct interactions with the N terminus. Axon injury activates SARM1 by releasing the auto-inhibition on the TIR domains. Activated TIRs then cleave NAD+ into Nam, ADPR and cADPR and trigger axon degeneration.