ADP-ribose pyrophosphatase, mitochondrial (NUDT9)

ADP-ribose pyrophosphatase, mitochondrial (NUDT9) is a monomeric enzyme of the Nudix hydrolase family, functioning primarily in the mitochondria. It catalyzes the hydrolysis of ADP-ribose to AMP and ribose 5-phosphate, requiring divalent metal ions and an intact Nudix motif. NUDT9 exhibits remarkable substrate specificity for ADP-ribose and is critical for regulating intracellular levels of this molecule, maintaining cellular metabolic balance, and protecting cells from toxicity due to accumulation of nucleotide derivatives. Additionally, NUDT9’s activity impacts the gating of the TRPM2 channel, linking it to Ca²⁺-dependent apoptotic signaling. Alternative splicing generates mitochondrial (alpha) and non-mitochondrial (beta) isoforms, distributed in tissues including heart, skeletal muscle, liver, kidney, and pancreas.

Other names

Nudix hydrolase 9ADPR-PPaseNUDT10 (occasionally used, but less common)Adenosine diphosphoribose pyrophosphataseADP-ribose diphosphataseNucleoside diphosphate-linked moiety X motif 9MGC3037NUDT9H (for TRPM2 domain homology, but not an isoform)PSEC0099, UNQ3012/PRO9771 (less common)

Substrate-mimetic inhibition of ADP-ribose hydrolysis (potential mechanism of candidate inhibitors). Indirect modulation of TRPM2 channel activity by altering ADPR levels.