Adult; Age of Onset; Aged; Cell Line, Tumor; DNA Mutational Analysis; Female; Genetic Predisposition to Disease/genetics; Genotype; HSP70 Heat-Shock Proteins/genetics; Humans; Male; Middle Aged; Mitochondria/metabolism; Mutation/genetics; Neuroblastoma/pathology; Oxygen Consumption/genetics; Parkinson Disease/genetics/pathology; Transfection; Young Adult; Early-onset Parkinson disease; GRP75; HSPA9; Mitochondria; Mortalin
Résumé :
[en] Dysfunctional mitochondria and the mitochondrial chaperone mortalin (HSPA9, GRP75) have been implicated in the pathogenesis of Parkinson disease (PD). We screened 139 early-onset PD (EOPD) patients for mutations in mortalin revealing one missense change (p.L358P) that was absent in 279 control individuals. We also found one additional missense variant among the controls (p.T333K). Although both missense changes were predicted to be disease causing, we detected no differences in subcellular localization, mitochondrial morphology, or respiratory function between wild-type and mutant mortalin. These findings suggest that variants in mortalin (1) are not a major cause of EOPD; (2) occur in patients and controls; and (3) do not lead to functional impairment of mitochondria.
