Publications by authors named "Gabriella Fiorino"
The 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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- Opioid overdose, a major cause of drug-related deaths, necessitates research into its mechanisms, particularly focusing on the preBötzinger Complex (preBötC) in the brain responsible for breathing regulation.
- This study successfully creates a protocol to derive preBötC-like neurons from human induced pluripotent stem cells (iPSCs), demonstrating their specific markers and expected functions.
- The research finds that these neurons exhibit dose-dependent responses to opioids and can be revived with naloxone, paving the way for further exploration of opioid-induced respiratory depression and potential treatments.
The ubiquitin (Ub) kinase-ligase pair PINK1-PRKN mediates the degradation of damaged mitochondria by macroautophagy/autophagy (mitophagy). PINK1 surveils mitochondria and upon stress accumulates on the mitochondrial surface where it phosphorylates serine 65 of Ub to activate PRKN and to drive mitochondrial turnover. While loss of either PINK1 or PRKN is genetically linked to Parkinson disease (PD) and activating the pathway seems to have great therapeutic potential, there is no formal proof that stimulation of mitophagy is always beneficial.
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