Calcitriol increases frataxin levels and restores mitochondrial function in cell models of Friedreich Ataxia

Friedreich ataxia (FA) is a neurodegenerative disease caused by the deficiency of frataxin, mitochondrial protein. In primary cultures dorsal root ganglia neurons, we showed that frataxin depletion resulted in decreased levels calcium exchanger NCLX, neurite degeneration and apoptotic cell death. Here, describe frataxin-deficient neurons display low ferredoxin 1 (FDX1), Fe/S cluster-containing protein interacts with and, interestingly, essential for synthesis calcitriol, active form vitamin D. We provide data calcitriol supplementation, used at nanomolar concentrations, able to reverse molecular cellular markers altered DRG neurons. Calcitriol recover both FDX1 NCLX restores membrane potential indicating an overall function improvement. Accordingly, reduction was observed as result, survival also recovered. All these beneficial effects would be explained finding increase mature both, cardiomyocytes; remarkably, this occurs lymphoblastoid lines derived from FA patients. conclusion, results bases consider easy affordable therapeutic approach