Department of Neurology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.
Department of Neurology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.
Neuron. 2022 Aug 3;110(15):2386-2408. doi: 10.1016/j.neuron.2022.04.020. Epub 2022 May 12.
The defining evolutionary feature of eukaryotic cells is the emergence of membrane-bound organelles. Compartmentalization allows each organelle to maintain a spatially, physically, and chemically distinct environment, which greatly bolsters individual organelle function. However, the activities of each organelle must be balanced and are interdependent for cellular homeostasis. Therefore, properly regulated interactions between organelles, either physically or functionally, remain critical for overall cellular health and behavior. In particular, neuronal homeostasis depends heavily on the proper regulation of organelle function and cross talk, and deficits in these functions are frequently associated with diseases. In this review, we examine the emerging role of organelle contacts in neurological diseases and discuss how the disruption of contacts contributes to disease pathogenesis. Understanding the molecular mechanisms underlying the formation and regulation of organelle contacts will broaden our knowledge of their role in health and disease, laying the groundwork for the development of new therapies targeting interorganelle cross talk and function.
真核细胞的一个定义性进化特征是出现膜结合细胞器。区室化使每个细胞器能够维持在空间上、物理上和化学上不同的环境，这极大地增强了单个细胞器的功能。然而，每个细胞器的活动必须保持平衡，并相互依赖以维持细胞内环境稳定。因此，细胞器之间的适当调节相互作用，无论是物理上还是功能上，对于整体细胞健康和行为仍然至关重要。特别是，神经元内环境稳定严重依赖于细胞器功能和串扰的适当调节，这些功能的缺陷经常与疾病有关。在这篇综述中，我们研究了细胞器接触在神经疾病中的新作用，并讨论了接触的破坏如何导致疾病的发病机制。了解细胞器接触形成和调节的分子机制将拓宽我们对其在健康和疾病中的作用的认识，为针对细胞器间串扰和功能的新疗法的发展奠定基础。
