Mitophagy Failure in Fibroblasts and iPSC-Derived Neurons of Alzheimer's Disease-Associated Presenilin 1 Mutation.

ABSTRACT: Familial Alzheimer's disease (FAD) is clearly related with the accumulation of amyloid-beta (Aβ) and its deleterious effect on mitochondrial function is well established. Anomalies in autophagy have also been described in these patients. In the present work, functional analyses have been performed to study mitochondrial recycling process in patient-derived fibroblasts and neurons from induced pluripotent stem cells harboring the presenilin 1 mutation A246E. Mitophagy impairment was observed due to a diminished autophagy degradation phase associated with lysosomal anomalies, thus causing the accumulation of dysfunctional mitochondria labeled by Parkin RBR E3 ubiquitin protein ligase (PARK2). The failure of mitochondrial recycling by autophagy was enhanced in the patient-derived neuronal mod

SUBMITTER: Martin-Maestro P 

PROVIDER: S-EPMC5603661 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature