中国科学技术大学生命科学与医学部熊伟教授与仓春蕾教授课题组合作取得一项新突破。他们完成了单溶酶体的代谢组学分析。该研究于2021年6月14日发表于国际学术期刊《自然-方法学》杂志。

研究人员构建了一个单溶酶体代谢组质谱 (SLMS) 平台，该平台集成了溶酶体膜片钳记录和诱导纳米电喷雾电离 (nanoESI)/质谱 (MS)，能够同时对个体单个溶酶体进行代谢和电生理分析。该技术的准确性和可靠性可通过对先前发现进行重复而得到验证，例如溶酶体阳离子氨基酸转运蛋白（如PQLC2）的可转运性和溶酶体对营养物质的捕获、如利多卡因等疏水性弱碱药物的发现。

研究人员从各种细胞类型的单个溶酶体中提取代谢物，并根据它们的化学和生物学差异将溶酶体分为五个主要亚群。衰老和癌症以特定类型的方式改变了溶酶体的代谢特征。因此，SLMS 可以为研究生理和病理过程中溶酶体代谢的变化提供更多的分析途径。 

研究人员表示，溶酶体对细胞代谢至关重要，并广泛参与各种细胞过程。检测溶酶体代谢异质性对于理解它们的生理作用至关重要。

附：英文原文

Title: Metabolomic profiling of single enlarged lysosomes

Author: Hongying Zhu, Qianqian Li, Tiepeng Liao, Xiang Yin, Qi Chen, Ziyi Wang, Meifang Dai, Lin Yi, Siyuan Ge, Chenjian Miao, Wenping Zeng, Lili Qu, Zhenyu Ju, Guangming Huang, Chunlei Cang, Wei Xiong

Issue&Volume: 2021-06-14

Abstract: Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes. Single-lysosome mass spectrometry (SLMS) integrates lysosomal patch-clamp recording and induced nanoESI/MS for concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes.

DOI: 10.1038/s41592-021-01182-8

Source: https://www.nature.com/articles/s41592-021-01182-8