Functional multi-organelle units control inflammatory lipid metabolism of macrophages

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

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• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature cell biology. - 26, 8 (2024) , 1261-1273, ISSN: 1476-4679

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2025
• Creator: Zimmermann, Julia ; Lucht, Kerstin ; Stecher, Manuel ; Badhan, Chahat ; Glaser, Katharina M. ; Epple, Maximilian W. ; Koch, Lena ; Deboutte, Ward ; Manke, Thomas ; Ebnet, Klaus ; Brinkmann, Frauke ; Fehler, Olesja ; Vogl, Thomas J. ; Schuster, Ev-Marie Christine ; Bremser, Anna ; Buescher, Joerg ; Rambold, Angelika

Further information

• DOI: 10.1038/s41556-024-01457-0
• URN: urn:nbn:de:bsz:25-freidok-2614546
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.