Quantitative proteomics in Friedreich's ataxia B-lymphocytes: A valuable approach to decipher the biochemical events responsible for pathogenesis
| Autor: | Emmanuel Lesuisse, Bastien Morlet, Jean-Michel Camadro, Lorène Télot, Valérie Serre, Elodie Rousseau, Camille Garcia, Thibaut Léger |
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| Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell physiology Proteomics Ataxia Proteome [SDV]Life Sciences [q-bio] Quantitative proteomics Mitochondrial Membrane Transport Proteins Pathogenesis 03 medical and health sciences Mitochondrial Precursor Protein Import Complex Proteins medicine Humans Molecular Biology B-Lymphocytes biology Lipid metabolism 3. Good health Cell biology 030104 developmental biology MESH: Frataxin Friedreich's ataxia Mitochondrial metabolism Friedreich Ataxia Frataxin biology.protein Molecular Medicine medicine.symptom Biogenesis |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2018, 1864 (4), pp.997-1009. ⟨10.1016/j.bbadis.2018.01.010⟩ |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2018.01.010⟩ |
| Popis: | International audience; Friedreich's ataxia (FRDA) represents the most frequent type of autosomal-recessively inherited ataxia and is caused by the deficiency of frataxin, a mitochondrial protein. It is known that frataxin-deficiency leads to alterations in cellular and mitochondrial iron metabolism and impacts in the cell physiology at several levels. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. Currently, cellular antioxidant defense is dysregulated when frataxin is deficient, which exacerbates oxidative damage in FRDA. Moreover, alterations in lipid metabolism have been observed in several models of the disease. To better understand the biochemical sequelae of frataxin reduction, global protein expression analysis was performed using quantitative proteomic experiments in Friedreich's ataxia patient-derived B-lymphocytes as compared to controls. We were able to confirm a subset of changes in these cells and importantly, we observed previously unreported signatures of protein expression. Among the novel protein signatures that we have identified, the decrease in CHCHD4 might partly explain some aspects of the molecular pathogenesis of FRDA. The identification of a core set of proteins changing in the FRDA pathogenesis is a useful tool in trying to decipher the function(s) of frataxin in order to clarify the mitochondrial metabolic disease process. |
| Databáze: | OpenAIRE |
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