White adipocytes function as major energy reservoirs in humans by storing substantial amounts of triglycerides, and their dysfunction is associated with metabolic disorders; however, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generate a spatiotemporal proteomic atlas of human adipogenesis, which elucidates cellular remodelling as well as the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and highlights the coordinated regulation of protein localization and abundance during adipocyte formation. We identify compartment-specific regulation of protein levels and localization changes of metabolic enzymes to reprogramme branched-chain amino acids and one-carbon metabolism to provide building blocks and reduction equivalents. Additionally, we identify C19orf12 as a differentiation-induced adipocyte lipid droplet protein that interacts with the translocase of the outer membrane complex of lipid droplet-associated mitochondria and regulates adipocyte lipid storage by determining the capacity of mitochondria to metabolize fatty acids. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.
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PublikationstypArtikel: Journalartikel
DokumenttypWissenschaftlicher Artikel
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SchlagwörterAdipose Triglyceride Lipase; Protein; Dynamics; Localization; Number; Link
POF Topic(s)90000 - German Center for Diabetes Research 30201 - Metabolic Health 30203 - Molecular Targets and Therapies 30205 - Bioengineering and Digital Health
Forschungsfeld(er)Helmholtz Diabetes Center Enabling and Novel Technologies Genetics and Epidemiology
FörderungenSwedish Society for Medical Research European Foundation for the Study of Diabetes (Future Leader Award) Swedish Research Council ERC-SyG SPHERES Novo Nordisk Foundation MeRIAD consortium Knut and Alice Wallenbergs Foundation Centre for Innovative Medicine Helmholtz Zentrum Munchen - Deutsches Forschungszentrum fur Gesundheit und Umwelt (GmbH) Swedish Diabetes Foundation Stockholm County Council Strategic Research Programme in Diabetes at the Karolinska Institutet DFG BATenergy NBIA Suisse Hoffnungsbaum NBIA Disorders Association NBIA Poland German Centre for Diabetes Research German Research Foundation European Research Council (ERC-CoG ) Karolinska Institutet DFG Emmy Noether Novo Nordisk postdoctoral fellowship