Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues.

Autor: Kamp M; Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE, UK.; Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.; Department of Chemistry, Utrecht University, 3584 CH, Utrecht, The Netherlands., Surmacki J; Lodz University of Technology, Institute of Applied Radiation Chemistry, Laboratory of Laser Molecular Spectroscopy, Wroblewskiego 15, 93-590, Lodz, Poland., Segarra Mondejar M; Hutchison/MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, CB2 0XZ, UK.; CECAD, Joseph-Stelzmann-Straße 26, 50931, Cologne, Germany., Young T; Hutchison/MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, CB2 0XZ, UK., Chrabaszcz K; Institute of Nuclear Physics, Polish Academy of Sciences, Department of Experimental Physics of Complex Systems, Radzikowskiego 152, 31-342, Krakow, Poland., Joud F; Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK., Zecchini V; Hutchison/MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, CB2 0XZ, UK., Speed A; Hutchison/MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, CB2 0XZ, UK., Frezza C; Hutchison/MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, CB2 0XZ, UK. christian.frezza@uni-koeln.de.; CECAD, Joseph-Stelzmann-Straße 26, 50931, Cologne, Germany. christian.frezza@uni-koeln.de., Bohndiek SE; Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE, UK. seb53@cam.ac.uk.; Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK. seb53@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 25; Vol. 15 (1), pp. 5386. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1038/s41467-024-49403-w
Abstrakt: Aberrantly accumulated metabolites elicit intra- and inter-cellular pro-oncogenic cascades, yet current measurement methods require sample perturbation/disruption and lack spatio-temporal resolution, limiting our ability to fully characterize their function and distribution. Here, we show that Raman spectroscopy (RS) can directly detect fumarate in living cells in vivo and animal tissues ex vivo, and that RS can distinguish between Fumarate hydratase (Fh1)-deficient and Fh1-proficient cells based on fumarate concentration. Moreover, RS reveals the spatial compartmentalization of fumarate within cellular organelles in Fh1-deficient cells: consistent with disruptive methods, we observe the highest fumarate concentration (37 ± 19 mM) in mitochondria, where the TCA cycle operates, followed by the cytoplasm (24 ± 13 mM) and then the nucleus (9 ± 6 mM). Finally, we apply RS to tissues from an inducible mouse model of FH loss in the kidney, demonstrating RS can classify FH status. These results suggest RS could be adopted as a valuable tool for small molecule metabolic imaging, enabling in situ non-destructive evaluation of fumarate compartmentalization.
(© 2024. The Author(s).)
Databáze: MEDLINE
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