Adenosine 5′-diphosphoribose

Adenosine 5′-diphosphoribose (ADP ribose) is a nicotinamide adenine nucleotide (NAD⁺) metabolite. Adenosine 5′-diphosphoribose is the most potent and primary intracellular Ca²⁺-permeable cation TRPM2 channel activator. Adenosine 5′-diphosphoribose also can enhance autophagy^[1][2]. In Vitro:In mouse embryonic fibroblasts (MEFs), H₂O₂ treatment demonstrates that the activation of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) produced Adenosine 5′-diphosphoribose (ADP ribose), which is an activating signal for TRPM2 channels, thereby promoting Ca²⁺ elevation through extracellular Ca²⁺ influx and (or) lysosomal Ca²⁺ release. This process eventually activates early or late autophagy in response to different degrees of oxidative stress^[1][1].
TRPM2 channels are activated by binding of Adenosine 5′-diphosphoribose (ADP ribose) to the intracellular NUDT9-homology (NUDT9-H) domain unique to TRPM2 and located at its C terminus. In addition to ADPR, intracellular Ca²⁺ is an essential coactivator: TRPM2 channels open only in the combined presence of both ligands^[2].