Mitochondrial Deoxyguanosine Kinase Regulates NAD Biogenesis Independent of Mitochondria Complex I Activity.

Overexpression of DGUOK promotes mitochondria oxidative phosphorylation and lung adenocarcinoma progression. However, the role and mechanism of DGUOK in regulation of mitochondria function and lung cancer progression still poorly understood. Here we demonstrated that regulated NAD biogenesis. Depletion of the significantly decreased NAD level. Furthermore, knockout of the considerably reduced expression of the , a key molecule controlling NAD synthesis, at both mRNA and protein levels. Ectopic expression of the abrogated the effect of knockdown of on NAD. Notably, this regulation is independent of DGUOK -mediated mitochondria complex I activity. We also showed that NMNAT2 was highly expressed in lung adenocarcinoma and negatively correlated with the patient overall survival. Our study suggested that DGUOK regulates NAD in a NMNAT2 dependent manner and DGUOK-NMNAT2-NAD axis could be a potential therapeutic target in lung adenocarcinoma.