Quantitative proteomics in Friedreich's ataxia B-lymphocytes: A valuable approach to decipher the biochemical events responsible for pathogenesis.
Fiche publication
Date publication
avril 2018
Journal
Biochimica et biophysica acta. Molecular basis of disease
Auteurs
Membres identifiés du Cancéropôle Est :
Mr MORLET Bastien
Tous les auteurs :
Télot L, Rousseau E, Lesuisse E, Garcia C, Morlet B, Léger T, Camadro JM, Serre V
Lien Pubmed
Résumé
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.
Mots clés
Frataxin, Friedreich's ataxia, Mitochondrial metabolism, Quantitative proteomics
Référence
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):997-1009