Cross-talks between Metabolic and Translational Controls during Beige Adipocyte Differentiation

Daehwa Youn, Boseon Kim, Dahee Jeong, Ju Yeon Lee, Seha Kim, Dulguun Sumberzul, Rehna Paula Ginting, Min-Woo Lee, Ju Hwan Song, Ye Seul Park, Yumin Kim, Chang-Myung Oh, Mihye Lee () and Jun Cho ()
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Daehwa Youn: Gwangju Institute of Science and Technology (GIST)
Boseon Kim: Soonchunhyang University
Dahee Jeong: Gwangju Institute of Science and Technology (GIST)
Ju Yeon Lee: Korea Basic Science Institute
Seha Kim: Gwangju Institute of Science and Technology (GIST)
Dulguun Sumberzul: Gwangju Institute of Science and Technology (GIST)
Rehna Paula Ginting: Soonchunhyang University
Min-Woo Lee: Soonchunhyang University
Ju Hwan Song: Korea Basic Science Institute
Ye Seul Park: Korea Basic Science Institute
Yumin Kim: Gwangju Institute of Science and Technology (GIST)
Chang-Myung Oh: Gwangju Institute of Science and Technology (GIST)
Mihye Lee: Soonchunhyang University
Jun Cho: Gwangju Institute of Science and Technology (GIST)

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Whether and how regulatory events at the translation stage shape the cellular and metabolic features of thermogenic adipocytes is hardly understood. In this study, we report two hitherto unidentified cross-talk pathways between metabolic and translational regulation in beige adipocytes. By analysing temporal profiles of translation activity and protein level changes during precursor-to-beige differentiation, we found selective translational down-regulation of OXPHOS component-coding mRNAs. The down-regulation restricted to Complexes I, III, IV, and V, is coordinated with enhanced translation of TCA cycle genes, engendering distinct stoichiometry of OXPHOS and TCA cycle components and altering the related metabolic activities in mitochondria of thermogenic adipocytes. Our high-resolution description of ribosome positioning unveiled potentiated ribosome pausing at glutamate codons. The increased stalling is attributable to remodelled glutamate metabolism that decreases glutamates for tRNA charging during pan-adipocyte differentiation. The ribosome pauses decrease protein synthesis and mRNA stability of glutamate codon-rich genes, such as actin cytoskeleton-associated genes.

Date: 2025
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DOI: 10.1038/s41467-025-58665-x

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