Márton Judit, Fodor Tamás, Nagy Lilla, Vida András, Kis Gréta, Brunyánszki Attila, Antal Miklós, Lüscher Bernhard, Bai Péter
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
MTA-DE Cell Biology and Signaling Research Group, Debrecen, Hungary.
PLoS One. 2018 Jan 2;13(1):e0187789. doi: 10.1371/journal.pone.0187789. eCollection 2018.
Poly(ADP-ribose) polymerase (PARP)10 is a PARP family member that performs mono-ADP-ribosylation of target proteins. Recent studies have linked PARP10 to metabolic processes and metabolic regulators that prompted us to assess whether PARP10 influences mitochondrial oxidative metabolism. The depletion of PARP10 by specific shRNAs increased mitochondrial oxidative capacity in cellular models of breast, cervical, colorectal and exocrine pancreas cancer. Upon silencing of PARP10, mitochondrial superoxide production decreased in line with increased expression of antioxidant genes pointing out lower oxidative stress upon PARP10 silencing. Improved mitochondrial oxidative capacity coincided with increased AMPK activation. The silencing of PARP10 in MCF7 and CaCo2 cells decreased the proliferation rate that correlated with increased expression of anti-Warburg enzymes (Foxo1, PGC-1α, IDH2 and fumarase). By analyzing an online database we showed that lower PARP10 expression increases survival in gastric cancer. Furthermore, PARP10 expression decreased upon fasting, a condition that is characterized by increases in mitochondrial biogenesis. Finally, lower PARP10 expression is associated with increased fatty acid oxidation.
聚（ADP - 核糖）聚合酶（PARP）10是PARP家族成员，可对靶蛋白进行单ADP核糖基化。最近的研究将PARP10与代谢过程及代谢调节因子联系起来，这促使我们评估PARP10是否影响线粒体氧化代谢。在乳腺癌、宫颈癌、结直肠癌和外分泌胰腺癌的细胞模型中，通过特异性短发夹RNA（shRNA）耗尽PARP10可增加线粒体氧化能力。PARP10沉默后，线粒体超氧化物生成减少，同时抗氧化基因表达增加，表明PARP10沉默后氧化应激降低。线粒体氧化能力的改善与AMPK激活增加同时出现。在MCF7和CaCo2细胞中沉默PARP10可降低增殖率，这与抗瓦伯格酶（Foxo1、PGC - 1α、IDH2和富马酸酶）表达增加相关。通过分析一个在线数据库，我们发现PARP10表达降低可提高胃癌患者的生存率。此外，禁食时PARP10表达下降，禁食是以线粒体生物合成增加为特征的一种状态。最后，PARP10表达降低与脂肪酸氧化增加有关。
