Differentiation but not ALS mutations in FUS rewires motor neuron metabolism
| العنوان: | Differentiation but not ALS mutations in FUS rewires motor neuron metabolism |
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| المؤلفون: | Peter Carmeliet, Sarah-Maria Fendt, Matthieu Moisse, Katlijn Vints, Philip Van Damme, Adria Sicart, Bart Ghesquière, Catherine M. Verfaillie, Katrien De Bock, Christine Germeys, Raheem Fazal, Ann Swijsen, Tijs Vandoorne, Annelies Quaegebeur, Wenting Guo, Guy Eelen, Laura Fumagalli, Natalia V. Gounko, Ludo Van Den Bosch, Koen Veys |
| المصدر: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications, 10 (1) |
| بيانات النشر: | Nature Publishing Group UK, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cellular differentiation, General Physics and Astronomy, Mitochondrion, medicine.disease_cause, LACTATE, AMYOTROPHIC-LATERAL-SCLEROSIS, 0302 clinical medicine, MITOCHONDRIA, Amyotrophic lateral sclerosis, Induced pluripotent stem cell, lcsh:Science, PHOSPHORYLATION, Motor Neurons, Mutation, Multidisciplinary, Cell Differentiation, DEGENERATION, Cell biology, Mitochondria, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, PYRUVATE CARBOXYLATION, Stem cell, STEM-CELLS, Glycolysis, BRAIN ENERGY-METABOLISM, Science, GLYCOLYSIS, Cell Respiration, Induced Pluripotent Stem Cells, Biology, Molecular neuroscience, General Biochemistry, Genetics and Molecular Biology, Article, MECHANISMS, 03 medical and health sciences, medicine, Humans, Lactic Acid, Neurodegeneration, Science & Technology, Amyotrophic Lateral Sclerosis, General Chemistry, Motor neuron, medicine.disease, Cellular neuroscience, Metabolic Flux Analysis, 030104 developmental biology, Glucose, Case-Control Studies, RNA-Binding Protein FUS, lcsh:Q, 030217 neurology & neurosurgery |
| الوصف: | Energy metabolism has been repeatedly linked to amyotrophic lateral sclerosis (ALS). Yet, motor neuron (MN) metabolism remains poorly studied and it is unknown if ALS MNs differ metabolically from healthy MNs. To address this question, we first performed a metabolic characterization of induced pluripotent stem cells (iPSCs) versus iPSC-derived MNs and subsequently compared MNs from ALS patients carrying FUS mutations to their CRISPR/Cas9-corrected counterparts. We discovered that human iPSCs undergo a lactate oxidation-fuelled prooxidative metabolic switch when they differentiate into functional MNs. Simultaneously, they rewire metabolic routes to import pyruvate into the TCA cycle in an energy substrate specific way. By comparing patient-derived MNs and their isogenic controls, we show that ALS-causing mutations in FUS did not affect glycolytic or mitochondrial energy metabolism of human MNs in vitro. These data show that metabolic dysfunction is not the underlying cause of the ALS-related phenotypes previously observed in these MNs. Nature Communications, 10 (1) ISSN:2041-1723 |
| وصف الملف: | Electronic; application/application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8afb09c5b6129302ad71256377af987eTest http://europepmc.org/articles/PMC6742665Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8afb09c5b6129302ad71256377af987e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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