Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities.
Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities.
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融合或裂变：线粒体在不同严重性的脑外伤中的命运。
DOI：
10.1038/s41598-017-09587-2
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发表时间：
2017-08-23
影响因子：
4.6
通讯作者：
Belli A
中科院分区：
文献类型：
--
作者：
Di Pietro V;Lazzarino G;Amorini AM;Signoretti S;Hill LJ;Porto E;Tavazzi B;Lazzarino G;Belli A
线粒体动力学是由代表线粒体质量控制(MQC)的复杂蛋白质系统调节的。MQC平衡融合和分裂的对立力量，决定线粒体和细胞的命运。在一些神经系统疾病中，功能障碍的线粒体显示了MQC基因和蛋白表达的显著变化，并参与了细胞损伤的病理生理机制。在本研究中，我们研究了不同严重程度的创伤性脑损伤大鼠MQC中的主要基因和蛋白的表达。分别于伤后6、24、48、120 检测脑组织匀浆中融合和分裂基因和蛋白的表达。与完整的脑对照组相比，结果显示，在mTBI中，导致融合或裂变的基因和蛋白质分别上调和下调，而在sTBI中，则分别下调和上调。特别是，调控内膜动力学、脊重塑、氧化磷酸化的OPA1被翻译后切割，在mTBI和sTBI中产生不同数量的长OPA1和短OPA1。与柠檬酸合成酶相关的数据证实，这些结果证实了一过性(MTBI)或永久性(STBI)线粒体功能障碍，增强了MQC对维持细胞功能的重要性，并表明OPA1是治疗TBI的一个有吸引力的潜在治疗靶点。
Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.
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影响因子：
5.3
作者：
Delettre, C;Griffoin, JM;Hamel, CP
通讯作者：
Hamel, CP
影响因子：
4.1
作者：
Hobbs, Jonathan G.;Young, Jacob S.;Bailes, Julian E.
通讯作者：
Bailes, Julian E.
影响因子：
4.8
作者：
Jahani-Asl, Arezu;Pilon-Larose, Karine;Slack, Ruth S.
通讯作者：
Slack, Ruth S.
DOI：
10.1073/pnas.1409952112
发表时间：
2015-04-21
影响因子：
11.1
作者：
Barrio, Jorge R.;Small, Gary W.;Kepe, Vladimir
通讯作者：
Kepe, Vladimir
影响因子：
4.1
作者：
FODA, MAA;MARMAROU, A
通讯作者：
MARMAROU, A