北京大学Xiao-Wei Chen、Xiao Wang研究团队发现，锰通过调节衣壳蛋白复合体II（COPII）缩合控制循环脂质稳态。相关论文于2023年10月26日发表在《自然—细胞生物学》杂志上。

研究人员发现COPII利用锰调节、自发的缩合来选择性地驱动脂蛋白输送并调控体内脂质平衡。然而，腺病毒会劫持基于缩聚的运输机制，从而使细胞膜锰转换为特殊的控制信号。锰直接与COPII内膜结合，并增强其凝结，从而改变了转运机制与动力学平衡。

锰可从线粒体储存中获取，对COPII发出信号，并以独特的功能形式选择性地控制脂蛋白分泌。因此，锰的膳食滴定可实现个性化血脂管理，从而对抗病理性血脂异常和动脉粥样硬化，这意味着一种具有广泛治疗潜力的凝结靶向策略可促进心血管代谢健康。

据了解，精确控制循环脂质对健康和疾病都至关重要。由特殊脂蛋白携带的大量脂质最初通过COPII分泌到血液循环中。目前尚不清楚通用COPII如何容纳丰富但非常规的脂蛋白，更不用说其在治疗转化种的应用。

附：英文原文

Title: Manganese regulation of COPII condensation controls circulating lipid homeostasis

Author: Wang, Xiao, Huang, Runze, Wang, Yawei, Zhou, Wenjing, Hu, Yating, Yao, Yuanhang, Cheng, Kunlun, Li, Xin, Xu, Bolin, Zhang, Jie, Xu, Yaowen, Zeng, Fanxin, Zhu, Yuangang, Chen, Xiao-Wei

Issue&Volume: 2023-10-26

Abstract: Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.

DOI: 10.1038/s41556-023-01260-3

Source: https://www.nature.com/articles/s41556-023-01260-3