Loss of Sacsin Protein Affects Cellular Metabolism
Author Information
Author(s): Perna Laura, Salsbury Grace, Dushti Mohammed, Smith Christopher J., Morales Valle, Bianchi Katiuscia, Czibik Gabor, Chapple J. Paul
Primary Institution: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London
Hypothesis
Mitochondrial metabolism would be disrupted by the loss of sacsin protein.
Conclusion
The study shows that loss of sacsin leads to increased aerobic glycolysis and altered glutamine metabolism in cells.
Supporting Evidence
- Sacsin knockout cells showed increased lactate production and decreased glucose levels compared to controls.
- Principal component analysis demonstrated clear segregation between control and sacsin knockout samples.
- Neuronal differentiation did not change the pattern of reduced intracellular glucose and increased lactate levels in sacsin knockout cells.
Takeaway
When a protein called sacsin is missing, cells change how they use energy, making more lactate and using less glucose.
Methodology
Mass spectrometry-based tracer analysis was performed using glucose- and glutamine-traced carbon to compare metabolite profiles between wild-type and sacsin-knockout cell lines.
Limitations
Rescue experiments in the knockout cell line were not performed due to the large size of sacsin, and less abundant metabolites may not have been detected accurately.
Statistical Information
P-Value
0.0768
Statistical Significance
p<0.1
Digital Object Identifier (DOI)
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