Calmodulin-dependent protein kinase II (CaMKII) mediates radiation-induced mitochondrial fission by regulating the phosphorylation of dynamin-related protein 1 (Drp1) at serine 616
Calmodulin-dependent protein kinase II (CaMKII) mediates radiation-induced mitochondrial fission by regulating the phosphorylation of dynamin-related protein 1 (Drp1) at serine 616
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DOI：
10.1016/j.bbrc.2017.12.012
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发表时间：
2018-01-08
影响因子：
3.1
通讯作者：
Inanami, Osamu
中科院分区：
文献类型：
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作者：
Bo, Tomoki;Yamamori, Tohru;Inanami, Osamu
线粒体动力学被认为是必不可少的维持细胞的质量和功能，以应对各种压力。虽然电离辐射（IR）刺激线粒体分裂，这是由线粒体分裂蛋白，动力蛋白相关蛋白1（Drp1）介导的，但目前尚不清楚IR如何促进Drp1激活和随后的线粒体分裂。因此，我们进行了这项研究，以调查这些问题。首先，我们发现X射线照射触发了Drp1在丝氨酸616（S616）的磷酸化，但没有在丝氨酸637（S637）。重建分析表明，野生型（WT）Drp1的引入恢复辐射诱导的线粒体分裂，这是缺乏Drp1缺陷的细胞。与转染WT或S637A Drp1的细胞相比，在S616A Drp1转染的细胞中，照射后线粒体形状的变化减轻。此外，抑制CaMKII显着抑制Drp1 5616磷酸化和线粒体分裂诱导的IR。这些结果表明，Drp1磷酸化在S616，而不是在5637，是辐射诱导线粒体分裂的先决条件，CaMKII调节Drp1磷酸化在5616照射后。(C)2017爱思唯尔公司All rights reserved.
Mitochondrial dynamics are suggested to be indispensable for the maintenance of cellular quality and function in response to various stresses. While ionizing radiation (IR) stimulates mitochondrial fission, which is mediated by the mitochondrial fission protein, dynamin-related protein 1 (Drp1), it remains unclear how IR promotes Drp1 activation and subsequent mitochondrial fission. Therefore, we conducted this study to investigate these concerns. First, we found that X-irradiation triggered Drp1 phosphorylation at serine 616 (S616) but not at serine 637 (S637). Reconstitution analysis revealed that introduction of wild-type (WT) Drp1 recovered radiation-induced mitochondrial fission, which was absent in Drp1-deficient cells. Compared with cells transfected with WT or S637A Drp1, the change in mitochondrial shape following irradiation was mitigated in S616A Drp1-transfected cells. Furthermore, inhibition of CaMKII significantly suppressed Drp1 5616 phosphorylation and mitochondrial fission induced by IR. These results suggest that Drp1 phosphorylation at S616, but not at 5637, is prerequisite for radiation induced mitochondrial fission and that CaMKII regulates Drp1 phosphorylation at 5616 following irradiation. (C) 2017 Elsevier Inc. All rights reserved.