A spatiotemporal proteomic map of human adipogenesis.
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Authors
Felix Klingelhuber; Scott Frendo-Cumbo; Muhmmad Omar-Hmeadi; Lucas Massier; Pamela Kakimoto; Austin J Taylor; Morgane Couchet; Sara Ribicic; Martin Wabitsch; Ana C Messias; Arcangela Iuso; Timo D Müller; Mikael Rydén; Niklas Mejhert; Natalie KrahmerAbstract
OBJECTIVE
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.
Source
Nature metabolism
Pub Types(s)
Journal Article
Language
English
PubMed ID
38565923