title: Stressed cybrids model demyelinated axons in multiple sclerosis.
abstract: Multiple sclerosis is likely caused by a complex interaction of multiple genes and environmental factors. The contribution of mitochondrial DNA genetic backgrounds has been frequently reported. To evaluate the effect of mitochondrial DNA haplogroups in the same genetic and environmental circumstances, we have built human transmitochondrial cell lines and simulated the effect of axon demyelination, one of the hallmarks of multiple sclerosis pathology, by altering the ionic gradients through the plasmalemma and increasing ATP consumption. In this model, mitochondrial biogenesis is observed. This process is larger in Uk cybrids, which mirrors their lower oxidative phosphorylation capacity in basal conditions. This model replicates a process occurring in both patients suffering from multiple sclerosis and several animal models of axon demyelination. Therefore, it can be used to analyze the contribution of various mitochondrial DNA genotypes to multiple sclerosis. In this sense, a longer or stronger energy stress, such as that associated with demyelinated axons in multiple sclerosis, could make Uk individuals more susceptible to this pathology. Finally, pharmacologic compounds targeted to mitochondrial biogenesis could be a potential therapy for multiple sclerosis.
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER) Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Llobet
authors.forename: Aurora
authors.initials: A
authors.lastname: Gómez-Durán
authors.forename: Ruth
authors.initials: R
authors.lastname: Iceta
authors.forename: Eldris
authors.initials: E
authors.lastname: Iglesias
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín-Martínez
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Ara
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
mesh_terms: D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004272:DNA, Mitochondrial; D006239:Haplotypes; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial