Intramitochondrial proteostasis is directly coupled to α-synuclein and amyloid β1-42 pathologies.

ABSTRACT: Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in α-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates α-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect α-synuclein p

SUBMITTER: Lautenschlager J 

PROVIDER: S-EPMC7383368 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature