德国马克斯·普朗克免疫生物学和表观遗传学研究所Angelika S. Rambold团队近期取得重要工作进展，他们研究提出，多细胞器功能单元控制巨噬细胞的炎症脂质代谢。相关研究成果2024年7月5日在线发表于《自然—细胞生物学》杂志上。

据介绍，真核细胞包含几个膜分离的细胞器，以划分不同的代谢反应。然而，当细胞适应代谢途径以支持其发育、存活或效应器功能时，这些细胞器系统是如何协调的，目前尚不清楚。

研究人员开发了OrgaPlexing，这是一种多光谱细胞器成像方法，用于全面绘制六种关键代谢细胞器及其相互作用。研究人员对巨噬细胞进行了分析，巨噬细胞是一种在感知细菌和炎症刺激时进行快速代谢转换的免疫细胞。研究表明，脂滴（LD）是主要的炎症反应细胞器，与其他细胞器形成三向和四向相互作用。虽然具有内质网（ER）和线粒体（线粒体-ER-LD单元）的簇有助于为LD生长提供脂肪酸，但过氧化物酶体（线粒体-ER-过氧化物酶-LD单元）的额外募集支持脂肪酸从LD流出。对这些单元的单个成分的干扰对炎症脂质介质的合成具有直接的功能后果。

总之，这一研究表明，巨噬细胞形成功能性的多器官单位来支持代谢适应，并提供了一种识别细胞器代谢信号中枢的实验策略。

附：英文原文

Title: Functional multi-organelle units control inflammatory lipid metabolism of macrophages

Author: Zimmermann, Julia A., Lucht, Kerstin, Stecher, Manuel, Badhan, Chahat, Glaser, Katharina M., Epple, Maximilian W., Koch, Lena R., Deboutte, Ward, Manke, Thomas, Ebnet, Klaus, Brinkmann, Frauke, Fehler, Olesja, Vogl, Thomas, Schuster, Ev-Marie, Bremser, Anna, Buescher, Joerg M., Rambold, Angelika S.

Issue&Volume: 2024-07-05

Abstract: Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multi-spectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (mitochondria–ER–LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (mitochondria–ER–peroxisome–LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid mediator synthesis. Together, we show that macrophages form functional multi-organellar units to support metabolic adaptation and provide an experimental strategy to identify organelle-metabolic signalling hubs.

DOI: 10.1038/s41556-024-01457-0

Source: https://www.nature.com/articles/s41556-024-01457-0