Moreover, pathogenic Parkin mutations interfere with distinct steps of mitochondrial translocation, ubiquitylation and/or final clearance through mitophagy.

Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. In addition, the autophagic adaptor p62/SQSTM1 is recruited to mitochondrial clusters and is essential for the clearance of mitochondria. Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. PINK1 kinase activity and its mitochondrial localization sequence are prerequisites to induce translocation of the E3 ligase Parkin to depolarized mitochondria. Here, we reveal important mechanistic steps of a PINK1/Parkin-directed pathway linking mitochondrial damage, ubiquitylation and autophagy in non-neuronal and neuronal cells. However, their molecular contribution to pathogenesis remains unclear. Mutations in PINK1 and PARKIN are the most frequent causes of recessive Parkinson's disease. Pharmaceutics 13:N/A (2021).Parkinson's disease is the most common neurodegenerative movement disorder. Miniaturization and Automation of a Human In Vitro Blood-Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery. Staphylococcus aureus Panton-Valentine Leukocidin triggers an alternative NETosis process targeting mitochondria. Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells. Impaired mitochondrial quality control in Rett Syndrome. High-resolution spatiotemporal pHe and pO2 imaging in head and neck and oesophageal carcinoma cells. Publishing research using ab120081? Please let us know so that we can cite the reference in this datasheet.Īb120081 has been referenced in 33 publications.

What is cccp mean biology