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Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson's disease model.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-16 , DOI: 10.1038/s41419-019-2184-y
Ji-Eun Bae 1 , Gil Myung Kang 2 , Se Hee Min 3 , Doo Sin Jo 1, 4 , Yong-Keun Jung 5 , Keetae Kim 6 , Min-Seon Kim 3 , Dong-Hyung Cho 1, 4
Affiliation  

A primary cilium is an antenna-like structure on the cell surface that plays a crucial role in sensory perception and signal transduction. Mitochondria, the 'powerhouse' of the cell, control cell survival, and death. The cellular ability to remove dysfunctional mitochondria through mitophagy is important for cell survival. We show here that mitochondrial stress, caused by respiratory complex inhibitors and excessive fission, robustly stimulates ciliogenesis in different types of cells including neuronal cells. Mitochondrial stress-induced ciliogenesis is mediated by mitochondrial reactive oxygen species generation, subsequent activation of AMP-activated protein kinase and autophagy. Conversely, abrogation of ciliogenesis compromises mitochondrial stress-induced autophagy, leading to enhanced cell death. In mice, treatment with mitochondrial toxin, MPTP elicits ciliary elongation and autophagy in the substantia nigra dopamine neurons. Blockade of cilia formation in these neurons attenuates MPTP-induced autophagy but facilitates dopamine neuronal loss and motor disability. Our findings demonstrate the important role of primary cilia in cellular pro-survival responses during mitochondrial stress.

中文翻译:

原发性纤毛介导线粒体应激反应,以促进帕金森氏病模型中的多巴胺神经元存活。

初级纤毛是细胞表面的类天线结构,在感觉和信号转导中起着至关重要的作用。线粒体是细胞的“动力”,它控制着细胞的存活和死亡。通过线粒体去除功能异常的线粒体的细胞能力对于细胞存活很重要。我们在这里表明,由呼吸道复合物抑制剂和过度裂变引起的线粒体应激强烈刺激了包括神经元细胞在内的不同类型细胞的纤毛发生。线粒体应激诱导的纤毛发生是由线粒体活性氧的产生,AMP激活的蛋白激酶的后续活化和自噬介导的。相反,取消纤毛发生会损害线粒体应激诱导的自噬,导致细胞死亡增加。在老鼠中 用线粒体毒素治疗,MPTP会在黑质多巴胺神经元中引起睫状体伸长和自噬。这些神经元中纤毛形成的阻滞减弱了MPTP诱导的自噬,但促进了多巴胺神经元的丧失和运动障碍。我们的研究结果表明线粒体应激过程中初级纤毛在细胞存活前应答中的重要作用。
更新日期:2019-12-17
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