Cholesterol homeostasis is critical for cell function and human health. Cholesterol is heterogeneously distributed among cellular membranes, with the redistribution of endocytosed dietary cholesterol playing a pivotal role in the regulation of cholesterol homeostasis. While gaps remain in our understanding of intracellular dietary cholesterol transport, a highly complex network of pathways is starting to emerge, often involving inter-dependent vesicular and non-vesicular transport mechanisms. The last decade has seen a surge in interest in non-vesicular transport and inter-organellar communication at membrane contact sites. By providing platforms for protein interactions, signalling events, lipid exchange and calcium flux, membrane contact sites (MCS) are now appreciated as controlling the fate of large amounts of lipid and play central roles in the regulation and co-ordination of endocytic trafficking. Here, we review the role of MCS in multiple pathways for cholesterol export from the endocytic pathway and highlight the intriguing interplay between vesicular and non-vesicular transport mechanisms and relationship with neurodegenerative disease.

中文翻译：

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与内吞网络保持联系：接触对胆固醇转运的重要性。

胆固醇稳态对于细胞功能和人类健康至关重要。胆固醇在细胞膜中分布不均，内吞膳食胆固醇的重新分布在调节胆固醇稳态中起关键作用。虽然我们对细胞内膳食胆固醇转运的理解仍然存在差距，但高度复杂的途径网络开始出现，通常涉及相互依赖的囊泡和非囊泡转运机制。在过去的十年中，人们对膜接触部位的非囊泡运输和细胞器间通讯的兴趣激增。通过为蛋白质相互作用、信号事件、脂质交换和钙通量提供平台，膜接触位点 (MCS) 现在被认为控制大量脂质的命运，并在调节和协调内吞运输中发挥核心作用。在这里，我们回顾了 MCS 在从内吞途径输出胆固醇的多种途径中的作用，并强调了水泡和非水泡运输机制之间有趣的相互作用以及与神经退行性疾病的关系。