Parkin overexpression attenuates Aβ-induced mitochondrial dysfunction in HEK293 cells by restoring impaired mitophagy

Publication date: Available online 17 January 2020Source: Life SciencesAuthor(s): Hongmei Wang, Ting Zhang, Xuhua Ge, Jingjiong Chen, Yuwu Zhao, Jianliang FuAbstractAimsMitochondrial dysfunction is an early prominent feature of Alzheimer's disease (AD). In the present study, we sought to investigate whether defective mitophagy is tightly related to amyloid-β (Aβ)-induced mitochondrial dysfunction.Main methodsImmunofluorescence, western blot and transmission electron microscopy were used to examine mitophagy. Mitochondrial membrane potential was assessed using the JC-1 dye. Mitochondrial ROS was detected using MitoSOX™ Red staining.Key findingsAβ induced mitochondrial dysfunction in HEK293 cells. Moreover, Aβ induced an increase in parkin translocation to mitochondria and led to a drastic reduction in cytosolic parkin. Furthermore, Aβ-treated cells displayed a microtubule-associated protein 1 light chain 3 (LC3) punctate pattern and elevated mitochondrial LC3-II levels, suggesting the upregulation of mitophagy. Notably, Aβ induced the accumulation of mitochondrial p62, which was associated with impaired mitophagy. In addition, Aβ-treated cells exhibited fragmented or swollen mitochondria with severely decreased cristae. We then investigated whether overexpression of parkin could protect cells against Aβ-induced mitochondrial dysfunction. Interestingly, parkin overexpression inhibited Aβ-induced mitochondrial dysfunction. Besides, parkin overexpression increased cyto...
Source: Life Sciences - Category: Biology Source Type: research