Alpha-synuclein-associated changes in PINK1-PRKN-mediated mitophagy are disease context dependent.

ABSTRACT: Alpha-synuclein (αsyn) aggregates are pathological features of several neurodegenerative conditions including Parkinson disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA). Accumulating evidence suggests that mitochondrial dysfunction and impairments of the autophagic-lysosomal system can contribute to the deposition of αsyn, which in turn may interfere with health and function of these organelles in a potentially vicious cycle. Here we investigated a potential convergence of αsyn with the PINK1-PRKN-mediated mitochondrial autophagy pathway in cell models, αsyn transgenic mice, and human autopsy brain. PINK1 and PRKN identify and selectively label damaged mitochondria with phosphorylated ubiquitin (pS65-Ub) to mark them for degradation (mitophagy). We found that dise

SUBMITTER: Hou X 

PROVIDER: S-EPMC10467041 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature