Brain Science and Engineering Institute, Kyungpook National University, Daegu, 41566, Korea.
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
Cell Death Dis. 2019 Dec 16;10(12):952. doi: 10.1038/s41419-019-2184-y.
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.
一个初级纤毛是一个天线状的结构在细胞表面，在感觉感知和信号转导中起着至关重要的作用。线粒体，细胞的“动力源”，控制细胞的存活和死亡。细胞通过自噬去除功能失调的线粒体的能力对细胞的存活很重要。我们在这里表明，呼吸复合物抑制剂和过度分裂引起的线粒体应激，在包括神经元细胞在内的不同类型的细胞中强烈刺激纤毛发生。线粒体应激诱导的纤毛发生是由线粒体活性氧的产生、随后的 AMP 激活蛋白激酶和自噬的激活介导的。相反，纤毛发生的阻断会损害线粒体应激诱导的自噬，导致细胞死亡增加。在小鼠中，用线粒体毒素 MPTP 处理会引起黑质多巴胺神经元的纤毛伸长和自噬。在这些神经元中阻断纤毛形成会减弱 MPTP 诱导的自噬，但会促进多巴胺神经元的丢失和运动障碍。我们的研究结果表明，初级纤毛在细胞在受到线粒体应激时的生存反应中起着重要作用。
