Spatial sterol metabolism unveiled by stimulated Raman imaging

Frontiers in Chemistry

Chemistry

Yihui Zhou¹  Hyeon Jeong Lee¹  Hanlin Zhu²  Yongqing Zhang²  Delong Zhang²  Cunqi Ye³  Wen Fang³ 

[1] Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China;Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Interdisciplinary Centre for Quantum Information, Zhejiang University, Hangzhou, China;Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China;

关键词: stimulated Raman scattering (SRS) microscopy;    metabolite imaging;    biophysics;    cholesterol;    genetic engineering;    HMGCoA reductase;    yeast;   

DOI  :  10.3389/fchem.2023.1166313

 received in 2023-02-15, accepted in 2023-03-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

Spatiotemporal dynamics of small-molecule metabolites have gained increasing attention for their essential roles in deciphering the fundamental machinery of life. However, subcellular-level regulatory mechanisms remain less studied, particularly due to a lack of tools to track small-molecule metabolites. To address this challenge, we developed high-resolution stimulated Raman scattering (SRS) imaging of a genetically engineered model (GEM) to map metabolites in subcellular resolution. As a result, an unexpected regulatory mechanism of a critical metabolite, sterol, was discovered in yeast by amplifying the strength of vibrational imaging by genetic modulation. Specifically, isozymes of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were evident to promote ergosterol distribution to distinct subcellular locations, where ergosterol was enriched by a local HMGR-directed synthesis. The heterogeneity of this expression pattern thus provides new insights into sterol metabolism and related disease treatment strategies. These findings demonstrate SRS-GEM as a promising platform for new possibilities in investigating metabolic regulation, disease mechanisms, and biopharmaceutical research.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Zhou, Fang, Zhu, Ye, Zhang and Lee.