An organelle-specific photoactivation and dual-isotope labeling strategy reveals phosphatidylethanolamine metabolic flux

Article Article scientifique Article An organelle-specific photoactivation and dual-isotope labeling strategy reveals phosphatidylethanolamine metabolic flux eng 2023 2023-01-16 author Simon Clémence 0000-0002-1368-9551 Department of Biochemistry, NCCR Chemical Biology, University of Geneva Geneva 1205 Switzerland clemence.simon@univ-lille.fr. 935038 author Asaro Antonino 0000-0001-9610-5381 Department of Biochemistry, NCCR Chemical Biology, University of Geneva Geneva 1205 Switzerland clemence.simon@univ-lille.fr. 943049 author Feng Suihan 0000-0002-9205-0050 Unit of Chemical Biology and Lipid Metabolism, Center for Microbes, Development and Health (CMDH), Institut Pasteur of Shanghai, Chinese Academy of Sciences Shanghai 200031 China. 833791 author Riezman Howard 0000-0003-4680-9422 Department of Biochemistry, NCCR Chemical Biology, University of Geneva Geneva 1205 Switzerland clemence.simon@univ-lille.fr. 134430 Département de biochimie (CHIBI) 1687-1695 10.1039/d2sc06069h 36819876 2041-6520 PMC9930920 https://xlink.rsc.org/?DOI=D2SC06069H Phosphatidylethanolamine metabolism plays essential roles in eukaryotic cells but has not been completely investigated due to its complexity. This is because lipid species, unlike proteins or nucleic acids, cannot be easily manipulated at the single molecule level or controlled with subcellular resolution, two of the key factors toward understanding their functions. Here, we use the organelle-targeting photoactivation method to study PE metabolism in living cells with a high spatiotemporal resolution. Containing predefined PE structures, probes which can be selectively introduced into the ER or mitochondria were designed to compare their metabolic products according to their subcellular localization. We combined photo-uncaging with dual stable isotopic labeling to track PE metabolism in living cells by mass spectrometry analysis. Our results reveal that both mitochondria- and ER-released PE participate in phospholipid remodeling, and that PE methylation can be detected only under particular conditions. Thus, our method provides a framework to study phospholipid metabolism at subcellular resolution. Dewey 540 Fondation Leducq Science and Technology Commission of Shanghai Municipality 2019SHZDZX02 Human Frontier Science Program LT000552/2020-L Swiss National Science Foundation Function and regulation of sphingolipids and ether lipids 184949 CH Swiss National Science Foundation NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry (phase III) 185898 CH 39 Département de biochimie 144 false 768 Groupe Riezman 860 NCCR Chemical Biology Chemical science 14 7 62606fac-ae3c-4cd1-b83f-a16b56c6335f Article (Published version) Public Article_scientifique_from_unpaywall.pdf 1146570 application/pdf CC BY-NC 23316dd592a2ab9772720eaf50afb8e3148b1cd88a4e2c36832babff5d76ffb0 openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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An organelle-specific photoactivation and dual-isotope labeling strategy reveals phosphatidylethanolamine metabolic flux	Chemical science			2023	19	126

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