Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Disease Models and Standard Methodologies
2.2. Subcellular Fractionation of Cells and Tissues for Lysosome Enrichment
2.3. Proteomic Analysis
2.4. Development of a Scoring System for Lysosomal Proteins and Data Confidence
2.5. Detection and Quantification of Intracellular Lipids by Fluorescence Microscopy
2.6. Cell Treatment
2.7. Functional Studies on Zebrafish
3. Results
3.1. Proteomic Analysis and Bioinformatic Categorization
3.2. Validation of Selected DEP
3.3. Characterization of the Zebrafish cln5 Knockdown Model
3.4. In-Vitro Modulation of ROS Overproduction
3.5. Modulation of Locomotor Phenotype in the Zebrafish Model
3.6. Modulation of Lipid Overproduction
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Doccini, S.; Marchese, M.; Morani, F.; Gammaldi, N.; Mero, S.; Pezzini, F.; Soliymani, R.; Santi, M.; Signore, G.; Ogi, A.; et al. Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease. Cells 2022, 11, 1840. https://doi.org/10.3390/cells11111840
Doccini S, Marchese M, Morani F, Gammaldi N, Mero S, Pezzini F, Soliymani R, Santi M, Signore G, Ogi A, et al. Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease. Cells. 2022; 11(11):1840. https://doi.org/10.3390/cells11111840
Chicago/Turabian StyleDoccini, Stefano, Maria Marchese, Federica Morani, Nicola Gammaldi, Serena Mero, Francesco Pezzini, Rabah Soliymani, Melissa Santi, Giovanni Signore, Asahi Ogi, and et al. 2022. "Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease" Cells 11, no. 11: 1840. https://doi.org/10.3390/cells11111840
APA StyleDoccini, S., Marchese, M., Morani, F., Gammaldi, N., Mero, S., Pezzini, F., Soliymani, R., Santi, M., Signore, G., Ogi, A., Rocchiccioli, S., Kanninen, K. M., Simonati, A., Lalowski, M. M., & Santorelli, F. M. (2022). Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease. Cells, 11(11), 1840. https://doi.org/10.3390/cells11111840