DGUOK调节烟酰胺腺嘌呤二核苷酸生成

脱氧鸟苷激酶(Dguok)具有通过介导细胞线粒体自噬发挥调控巨噬细胞极化的功能,研究表明Dguok敲低后细胞自噬水平增强,LC-3B点状聚集增加,自噬小体数目显著上升,利用免疫荧光共定位的方法证实在Dguok干扰的细胞中线粒体自噬水平增强,说明Dguok干扰触发线粒体自噬。更加重要的是,Dguok敲低的Raw264.7细胞M1型相关指标几乎被完全抑制。IL-1,IL6,TNF-α,iNOS RNA以及蛋白水平表达均被显著抑制,表面marker CD11c的表达也降低。脱氧鸟苷激酶(DGUOK)的缺乏会导致mtDNA的耗竭和线粒体功能障碍,在此展示了DGUOK基因敲除(Dguok-/-)小鼠的长期生存的分子途径。

参考文献:

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Guo Jingyi,Duan Lifan,He Xueying et al. A Combined Model of Human iPSC-Derived Liver Organoids and Hepatocytes Reveals Ferroptosis in DGUOK Mutant mtDNA Depletion Syndrome.[J] .Adv Sci (Weinh), 2021, 8: 2004680.

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DGUOK控制mRNA中NMNAT2表达.和蛋白质水平

 

 

 

DGUOK敲除小鼠器官相对比重明显高于正常小鼠

DGUOK通过NMNAT2调节烟酰胺腺嘌呤二核苷酸生成

敲除DGUOK基因的小鼠模型建立过程图解

脂褐素在DGUOK敲除小鼠肝脏和皮肤出现积聚