The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process
The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process
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DOI：
10.1016/j.bbrc.2008.11.086
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发表时间：
2009-01-16
影响因子：
3.1
通讯作者：
Chung, Jongkyeong
中科院分区：
文献类型：
--
作者：
Park, Jeehye;Lee, Gina;Chung, Jongkyeong
两个帕金森病（PD）基因，PTEN诱导的激酶1（PINK 1）和parkin，在一个共同的途径，影响线粒体的完整性和功能。然而，目前还不知道这条通路在线粒体中起什么作用。因此，我们研究了它在果蝇中的生理功能。由于果蝇PINK 1和parkin突变体在间接飞行肌和多巴胺能神经元中显示线粒体形态的变化，我们在这里研究了PINK 1-Parkin通路是否与线粒体融合和分裂的调节因子（如促进线粒体分裂的Drp 1和诱导线粒体融合的Opal或Marf）发生遗传相互作用。令人惊讶的是，果蝇PINK 1和parkin突变体表型被Opal或Marf的Drp 1 OF下调的过表达显著抑制，表明PINK 1-Parkin通路在促进线粒体分裂的方向上调节线粒体重塑过程。因此，我们强烈建议线粒体融合和分裂过程可能是治疗PD的突出治疗靶点。(C)2008年爱思唯尔公司All rights reserved.
The two Parkinson's disease (PD) genes, PTEN-induced kinase 1 (PINK1) and parkin, are linked in a common pathway which affects mitochondrial integrity and function. However, it is still not known what this pathway does in the mitochondria. Therefore, we investigated its physiological function in Drosophila. Because Drosophila PINK1 and parkin Mutants show changes in mitochondrial morphology in both indirect flight muscles and dopaminergic neurons, we here investigated whether the PINK1-Parkin pathway genetically interacts with the regulators of mitochondrial fusion and fission such as Drp1, which promotes mitochondrial fission, and Opal or Marf, which induces mitochondrial fusion. Surprisingly, Drosophila PINK1 and parkin mutant phenotypes were markedly suppressed by overexpression of Drp1 OF downregulation of Opal or Marf, indicating that the PINK1-Parkin pathway regulates mitochondrial remodeling process in the direction of promoting mitochondrial fission. Therefore, we strongly suggest that mitochondrial fusion and fission process could be a prominent therapeutic target for the treatment of PD. (C) 2008 Elsevier Inc. All rights reserved.