济南大学林伟英团队利用双荧光寿命探针验证细胞器相互作用的调节机制。相关研究成果发表在2022年11月1日出版的国际学术期刊《美国化学会杂志》。

器官是动态的，但高度组织的，以保持细胞内稳态。然而，由于缺乏时间分辨的分子工具来同时对两个细胞器进行双信号成像，科学家们无法在纳秒时间尺度上阐明细胞器相互作用的调控机制。迄今为止，内质网（ER）和自噬体之间相互作用的调控机制尚不清楚。

该文中，研究人员提出了一种开发定位内质网和自噬体的双荧光寿命探针的策略，以研究它们的相互作用调节机制。使用稳健的探针CF2，研究人员研究了内质网和自噬体之间的调节机制，发现：（i）内质网末端的活动自噬小体驱动内质网小管生长和滑动；（ii）内质网小管形成以自噬体为中心的三通结；（iii）ER自噬是药物诱导凋亡过程中的一种细胞损伤指数。因此，该研究提高了人们对细胞器相互作用调节机制的认识，为确定神经退行性疾病的治疗靶点提供了依据。

附：英文原文

Title: Harnessing Dual-Fluorescence Lifetime Probes to Validate Regulatory Mechanisms of Organelle Interactions

Author: Yuping Zhao, Hyeong Seok Kim, Xiang Zou, Ling Huang, Xing Liang, Zihong Li, Jong Seung Kim, Weiying Lin

Issue&Volume: November 1, 2022

Abstract: Organelles are dynamic yet highly organized to preserve cellular homeostasis. However, the absence of time-resolved molecular tools for simultaneous dual-signal imaging of two organelles has prevented scientists from elucidating organelle interaction regulatory mechanisms on a nanosecond timescale. To date, the regulatory mechanisms governing the interaction between endoplasmic reticulum (ER) and autophagosomes are unknown. In this study, we propose a strategy for developing dual-fluorescence lifetime probes localized to the endoplasmic reticulum and autophagosomes to investigate their interaction regulatory mechanisms. Using the robust probe CF2, we investigated the regulatory mechanisms between ER and autophagosomes and discovered the following: (i) motile autophagosome in ER tips drives the ER tubule to grow and slide; (ii) the ER reticulate tubule forms a three-way junction centered on the autophagosome; (iii) ER autophagy is a type of cell damage index during drug-induced apoptosis. Thus, this study advances our knowledge of organelle interaction regulatory mechanisms, shedding light on the identification of therapeutic targets for neurodegenerative diseases.

DOI: 10.1021/jacs.2c08966

Source: https://pubs.acs.org/doi/10.1021/jacs.2c08966