αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson's disease.

ABSTRACT: The etiology of Parkinson's disease (PD) converges on a common pathogenic pathway of mitochondrial defects in which α-Synuclein (αSyn) is thought to play a role. However, the mechanisms by which αSyn and its disease-associated allelic variants cause mitochondrial dysfunction remain unknown. Here, we analyzed mitochondrial axonal transport and morphology in human-derived neurons overexpressing wild-type (WT) αSyn or the mutated variants A30P or A53T, which are known to have differential lipid affinities. A53T αSyn was enriched in mitochondrial fractions, inducing significant mitochondrial transport defects and fragmentation, while milder defects were elicited by WT and A30P. We found that αSyn-mediated mitochondrial fragmentation was linked to expression levels in WT and A53T variants. Targ

SUBMITTER: Pozo Devoto VM 

PROVIDER: S-EPMC5506004 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature