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

Author

Listed:
  • Marlous Kamp

    (University of Cambridge
    Robinson Way
    Utrecht University)

  • Jakub Surmacki

    (Laboratory of Laser Molecular Spectroscopy)

  • Marc Segarra Mondejar

    (University of Cambridge, Biomedical Campus
    CECAD)

  • Tim Young

    (University of Cambridge, Biomedical Campus)

  • Karolina Chrabaszcz

    (Department of Experimental Physics of Complex Systems)

  • Fadwa Joud

    (Robinson Way)

  • Vincent Zecchini

    (University of Cambridge, Biomedical Campus)

  • Alyson Speed

    (University of Cambridge, Biomedical Campus)

  • Christian Frezza

    (University of Cambridge, Biomedical Campus
    CECAD)

  • Sarah E. Bohndiek

    (University of Cambridge
    Robinson Way)

Abstract

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.

Suggested Citation

  • Marlous Kamp & Jakub Surmacki & Marc Segarra Mondejar & Tim Young & Karolina Chrabaszcz & Fadwa Joud & Vincent Zecchini & Alyson Speed & Christian Frezza & Sarah E. Bohndiek, 2024. "Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49403-w
    DOI: 10.1038/s41467-024-49403-w
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    References listed on IDEAS

    as
    1. Alexander Hooftman & Christian G. Peace & Dylan G. Ryan & Emily A. Day & Ming Yang & Anne F. McGettrick & Maureen Yin & Erica N. Montano & Lihong Huo & Juliana E. Toller-Kawahisa & Vincent Zecchini & , 2023. "Macrophage fumarate hydratase restrains mtRNA-mediated interferon production," Nature, Nature, vol. 615(7952), pages 490-498, March.
    2. Christian Frezza & Liang Zheng & Ori Folger & Kartik N. Rajagopalan & Elaine D. MacKenzie & Livnat Jerby & Massimo Micaroni & Barbara Chaneton & Julie Adam & Ann Hedley & Gabriela Kalna & Ian P. M. To, 2011. "Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase," Nature, Nature, vol. 477(7363), pages 225-228, September.
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