Publications by authors named "Bernardo A Bustillos"
Article Synopsis
- Mutations in the PRKN gene are a leading cause of early-onset Parkinson disease, with the p.R275W variant being the most common among patients.
- Research using patient fibroblasts, isogenic neurons, and human brain samples reveals that the p.R275W mutation significantly reduces PRKN protein levels, impairing mitophagy and mitochondrial degradation.
- Structural simulations indicate that this mutation destabilizes the PRKN protein, leading to a loss-of-function under normal biological conditions.
Mutations in PINK1 and Parkin cause early-onset Parkinson's Disease (PD). PINK1 is a kinase which functions as a mitochondrial damage sensor and initiates mitochondrial quality control by accumulating on the damaged organelle. There, it phosphorylates ubiquitin, which in turn recruits and activates Parkin, an E3 ubiquitin ligase.
View Article and Find Full Text PDFThe ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous conditions and especially in the brain remain undetermined.
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