AUTHOR=Sang Lei , He Ying-Jie , Kang Jiaxin , Ye Hongyi , Bai Weiyu , Luo Xiao-Dong , Sun Jianwei 

TITLE=Mitochondrial Deoxyguanosine Kinase Regulates NAD+ Biogenesis Independent of Mitochondria Complex I Activity

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.570656

DOI=10.3389/fonc.2020.570656

ISSN=2234-943X

ABSTRACT=<p>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 <italic>DGUOK</italic> regulated NAD<sup>+</sup> biogenesis. Depletion of the <italic>DGUOK</italic> significantly decreased NAD<sup>+</sup> level. Furthermore, knockout of the <italic>DGUOK</italic> considerably reduced expression of the <italic>NMNAT2</italic>, a key molecule controlling NAD<sup>+</sup> synthesis, at both mRNA and protein levels. Ectopic expression of the <italic>NMNAT2</italic> abrogated the effect of knockdown of <italic>DGUOK</italic> on NAD<sup>+</sup>. 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<sup>+</sup> in a NMNAT2 dependent manner and DGUOK-NMNAT2-NAD<sup>+</sup> axis could be a potential therapeutic target in lung adenocarcinoma.</p>