A spatiotemporal proteomic map of human adipogenesis

Sammanfattning

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.Klingelhuber, Frendo-Cumbo et al. develop a proteomic atlas elucidating the intracellular spatiotemporal changes in protein levels and localizations during human adipogenesis.

Publicerad i

Nature Metabolism
2024, volym: 6, nummer: 5, sidor: 861–879

SLU författare

• Omar Hmeadi, Muhmmad

  • Karolinska institutet

UKÄ forskningsämne

Biokemi och molekylärbiologi
Endokrinologi och diabetes

Publikationens identifierare

• DOI: https://doi.org/10.1038/s42255-024-01025-8

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/131833