Regulatory roles of hypoxia-inducible, noncoding RNAs on mitochondrial dynamics during AKI
Regulatory roles of hypoxia-inducible, noncoding RNAs on mitochondrial dynamics during AKI
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缺氧诱导的非编码 RNA 对 AKI 期间线粒体动力学的调节作用
DOI：
10.1016/j.kint.2018.12.002
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发表时间：
2019
影响因子：
19.6
通讯作者：
Nangaku Masaomi
中科院分区：
文献类型：
--
作者：
Tanaka Tetsuhiro;Nangaku Masaomi
线粒体动力学是细胞适应缺氧的一个组成部分。线粒体融合和分裂的动态、稳态控制通过参与融合（例如，线粒体融合蛋白-1和-2和视神经萎缩1 [OPA 1]）和分裂（例如，动力蛋白相关蛋白1 [DRP 1]和线粒体蛋白18 kDa [MTP 18]）的蛋白质活性进行微妙平衡。根据先前的研究，Drp 1的药理学抑制可预防急性肾损伤，1并且肾小管细胞中裂变蛋白的缺失可促进阿基的恢复并减轻纤维化，这意味着线粒体动力学的控制可作为潜在的治疗靶点。2线粒体融合/分裂蛋白的活性受翻译后修饰的调节，如去磷酸化和蛋白水解切割，而这些基因的转录/翻译控制在很大程度上是难以捉摸的，并提出了microRNA的调控机制。3低氧基因的表达主要由低氧诱导转录因子（HIF）家族介导。HIF的靶基因包括那些参与增加氧供应（如红细胞生成4和血管生成）和适应有限的氧需求（如糖酵解）的基因。除了蛋白质编码基因RNA，非编码RNA，如microRNA，和长的非编码RNA似乎也可被HIF诱导，5但这些观察结果的病理生理学相关性才刚刚开始被发现。6
Mitochondrial dynamics is an integral part of cellular adaptation to hypoxia. Dynamic, homeostatic control of mitochondrial fusion and fission is delicately balanced by the activity of proteins involved in fusion (eg, mitofusin-1 and-2, and optic atrophy 1 [OPA1]) and fission (eg, dynamin-related protein 1 [DRP1] and mitochondrial protein 18 kDa [MTP18]). According to preceding studies, pharmacological inhibition of Drp1 prevented acute kidney injury, 1 and deletion of a fission protein in tubular cells promoted recovery from AKI and attenuated fibrosis, signifying that the control of mitochondrial dynamics may serve as a potential therapeutic target. 2 The activity of mitochondrial fusion/fission proteins is regulated by posttranslational modification, such as de/phosphorylation and proteolytic cleavage, whereas the transcriptional/translational control of such genes is largely elusive and a regulatory mechanism by microRNAs is suggested. 3Hypoxic gene expression is primarily mediated by a family of hypoxia-inducible transcription factors (HIFs). Target genes of HIF include those involved in increasing oxygen supply (eg, erythropoiesis 4 and angiogenesis) and adapting to limited oxygen demand (eg, glycolysis). In addition to protein-coding gene RNAs, noncoding RNAs, such as microRNAs, and long noncoding RNAs appear to be also inducible by HIF, 5 but the pathophysiological relevance of these observations is only beginning to be uncovered. 6