Reconstruction of Molecular Interaction Patterns from Endolysosomes in Ceramide-Depleted Cells
Yiqing Feng1,2, Florian Gärber3, Cecilia Spedalieri1
1Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany.
Nano Letters
|May 4, 2026
Summary
Ceramide synthase inhibition disrupts cellular lipid homeostasis. Advanced nanospectroscopy and machine learning revealed distinct endolysosome changes, highlighting metabolic coupling between the ER and endolysosomes.
Area of Science:
- Biochemistry
- Cell Biology
- Biophysics
Background:
- Ceramide synthase (CerS) regulates sphingolipid metabolism and lipid homeostasis in the endoplasmic reticulum (ER).
- Understanding subcellular lipid flux and enzyme activity is crucial for deciphering cellular metabolic pathways.
Purpose of the Study:
- To investigate the biochemical and ultrastructural cellular consequences of CerS inhibition.
- To explore the metabolic coupling between the ER and endolysosomes in response to ceramide imbalance.
Main Methods:
- Utilized surface-enhanced Raman scattering (SERS) nanospectroscopy for biochemical analysis.
- Employed soft X-ray tomography for ultrastructural imaging.
- Applied random forest (RF) machine learning for spectral pattern analysis.
Main Results:
- Observed diverging alterations in endolysosomes and cellular ultrastructure upon CerS inhibition.
- RF analysis identified distinct spectral patterns in affected endolysosomes, indicative of ceramide imbalance.
- Demonstrated a tight metabolic coupling between the ER and endolysosomes.
Conclusions:
- Vibrational nanospectroscopy, tomography, and machine learning offer a comprehensive strategy for in situ analysis of enzyme activity.
- The study provides insights into metabolic dysregulation and lipid homeostasis disruption.
- Highlights the intricate relationship between ER lipid synthesis and endolysosomal function.
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