Impairing the mitochondrial fission and fusion balance: a new mechanism of neurodegeneration.
Impairing the mitochondrial fission and fusion balance: a new mechanism of neurodegeneration.
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DOI：
10.1196/annals.1427.030
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发表时间：
2008-12
影响因子：
5.2
通讯作者：
Bossy-Wetzel E
中科院分区：
文献类型：
--
作者：
Knott AB;Bossy-Wetzel E
线粒体功能障碍是所有神经退行性疾病的共同特征。然而，这种功能障碍的原因仍然是个谜。在这里，我们讨论线粒体裂变和融合在神经退行性疾病的发生和进展中的潜在作用。具体来说，我们提出线粒体裂变和融合的不平衡可能是家族性和散发性神经退行性疾病的基础。有大量证据表明，线粒体裂变和融合平衡的破坏（导致线粒体异常长或短）与神经变性有关。首先，线粒体融合 GTP 酶视神经萎缩-1 (OPA1) 和线粒体融合蛋白-2 (Mfn2) 的遗传性突变会导致人类神经病。此外，最近的研究结果报告了帕金森病 (PD) 模型中线粒体裂变的增加，以及 PTEN 诱导激酶 1 (PINK1) 和 Parkin 两种蛋白对线粒体裂变的诱导，这两种蛋白在帕金森病家族性形式中是突变的。此外，突变亨廷顿蛋白（亨廷顿病（HD）中的致病蛋白）会改变线粒体的形态和动力学。鱼藤酮（一种杀虫剂和 PD 症状诱导剂）和 β 淀粉样蛋白 (Aβ) 肽（与阿尔茨海默病 (AD) 存在因果关系）会启动线粒体裂变。最后，线粒体分裂是缺血性中风和糖尿病神经病变的早期事件。总之，越来越多的研究表明，更好地了解线粒体裂变和融合以及所涉及的调节因素可能会改善神经退行性疾病的治疗和治愈方法。
Mitochondrial dysfunction is a common characteristic of all neurodegenerative diseases. However, the cause of this dysfunction remains a mystery. Here, we discuss the potential role of mitochondrial fission and fusion in the onset and progression of neurodegenerative diseases. Specifically, we propose that an imbalance in mitochondrial fission and fusion may underlie both familial and sporadic neurodegenerative disorders. There is substantial evidence that links disruption of the mitochondrial fission and fusion equilibrium, resulting in abnormally long or short mitochondria, to neurodegeneration. First, hereditary mutations in the mitochondrial fusion GTPases optic atrophy-1 (OPA1) and mitofusin-2 (Mfn2) cause neuropathies in humans. In addition, recent findings report increased mitochondrial fission in Parkinson's disease (PD) models and induction of mitochondrial fission by two proteins, PTEN-induced kinase 1 (PINK1) and Parkin, which are mutant in familial forms of PD. Furthermore, mutant huntingtin, the disease-causing protein in Huntington's disease (HD), alters mitochondrial morphology and dynamics. Rotenone, a pesticide and inducer of PD symptoms, and amyloid-β (Aβ) peptide, which is causally linked to Alzheimer's disease (AD), initiate mitochondrial fission. Finally, mitochondrial fission is an early event in ischemic stroke and diabetic neuropathies. In sum, a growing body of research suggests that a better understanding of mitochondrial fission and fusion and the regulatory factors involved may lead to improved treatments and cures for neurodegenerative diseases.
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影响因子：
5.3
作者：
Crouch, PJ;Blake, R;Trounce, IA
通讯作者：
Trounce, IA
影响因子：
11.2
作者：
Biskup, Saskia;Moore, Darren J.;Dawson, Valina L.
通讯作者：
Dawson, Valina L.
影响因子：
4.8
作者：
Devi, Latha;Raghavendran, Vijayendran;Anandatheerthavarada, Hindupur K.
通讯作者：
Anandatheerthavarada, Hindupur K.
影响因子：
11.4
作者：
Barsoum, Mark J.;Yuan, Hua;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC