Version 1
: Received: 5 November 2024 / Approved: 6 November 2024 / Online: 7 November 2024 (07:19:21 CET)
How to cite:
Perna, L.; Salsbury, G.; Dushti, M.; Smith, C. J.; Morales, V.; Bianchi, K.; Czibik, G.; Chapple, J. P. Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin. Preprints2024, 2024110387. https://doi.org/10.20944/preprints202411.0387.v1
Perna, L.; Salsbury, G.; Dushti, M.; Smith, C. J.; Morales, V.; Bianchi, K.; Czibik, G.; Chapple, J. P. Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin. Preprints 2024, 2024110387. https://doi.org/10.20944/preprints202411.0387.v1
Perna, L.; Salsbury, G.; Dushti, M.; Smith, C. J.; Morales, V.; Bianchi, K.; Czibik, G.; Chapple, J. P. Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin. Preprints2024, 2024110387. https://doi.org/10.20944/preprints202411.0387.v1
APA Style
Perna, L., Salsbury, G., Dushti, M., Smith, C. J., Morales, V., Bianchi, K., Czibik, G., & Chapple, J. P. (2024). Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin. Preprints. https://doi.org/10.20944/preprints202411.0387.v1
Chicago/Turabian Style
Perna, L., Gabor Czibik and J Paul Chapple. 2024 "Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin" Preprints. https://doi.org/10.20944/preprints202411.0387.v1
Abstract
Mitochondrial dysfunction is implicated in the pathogenesis of the neurological condition Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay (ARSACS), yet precisely how mitochondrial metabolism is affected is unknown. Thus, to better understand changes in mitochondrial metabolism caused by loss of the sacsin protein (encoded by the SACS gene, that is mutated in ARSACS) we performed mass spectrometry-based tracer analysis, with both glucose and glutamine traced carbon. Comparing the metabolite profiles between wild-type and sacsin-knockout cell lines revealed increased reliance on aerobic glycolysis in sacsin-deficient cells, as evidenced by the increase in lactate and reduction of glucose. Moreover, sacsin knockout cells differentiated towards a neuronal phenotype had increased levels of tricarboxylic acid cycle metabolites relative to controls. We also observed disruption in the glutaminolysis pathway in differentiated and undifferentiated cells in the absence of sacsin. In conclusion, this work demonstrates consequences for cellular metabolism associated with loss of sacsin, which may be relevant to ARSACS.
Keywords
ARSACS; sacsin; mitochondria; metabolism
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
*
