Mitochondria-Endoplasmic Reticulum contact sites remodeling accompanies Luhmes differentiation

Neural progenitor cells (NPCs) are often used to study the subcellular mechanisms underlyingdifferentiation into neurons in vitro. Works published to date have focused on the pathways thatdistinguish undifferentiated NPCs from mature neurons, neglecting the earlier and intermediatestages of this process. Current evidence suggests that mitochondrial interaction with the ER isfundamental to a wide range of intracellular processes. However, it is not clear whether and how themitochodnrial interactions differ between NPC and their differentiated counterparts. Here we takeadvantage of the widely used NPC line Luhmes to characterize the subcellular changes occurringduring the first stage of their maturation into dopaminergic neurons to highlight the mitochondrialdynamics traits that accompany neuronal differentiation. We observed that the morphology ofmitochondria, their interaction with the ER and the expression of several mitochondria-ER contactsite resident proteins change, which suggests the potential contribution of mitochondria dynamics toNPC differentiation. Our findings may be relevant to the scientific community focusing onembryonic neurogenesis and developmental neurotoxicity.

神经前体细胞（Neural progenitor cells，NPCs）常被用于体外研究神经元分化的潜在亚细胞机制。迄今已发表的相关研究多聚焦于区分未分化神经前体细胞与成熟神经元的信号通路，却忽略了该过程的早期及中间阶段。现有研究证据表明，线粒体与内质网（Endoplasmic Reticulum，ER）的相互作用对诸多细胞内生命过程至关重要。然而，目前尚不清楚神经前体细胞与其分化子代之间，线粒体相互作用是否存在差异以及具体的调控机制。本研究借助目前广泛使用的神经前体细胞系Luhmes，对其向多巴胺能神经元成熟的初始阶段中发生的亚细胞变化进行系统表征，以揭示伴随神经元分化的线粒体动态特征。研究发现，线粒体的形态、其与内质网的相互作用，以及多种线粒体-内质网接触位点驻留蛋白的表达均发生显著改变，这提示线粒体动态变化可能在神经前体细胞分化过程中发挥潜在作用。本研究结果可为专注于胚胎神经发生与发育性神经毒性的科研群体提供有价值的参考。