Phosphorylaiton of ub and parkin in mitophagy
WebJan 1, 2024 · Phosphorylation of Ub attached to OMM substrates has several functional implications for mitophagy. First, pSer65-Ub serves as a potent Parkin receptor to recruit … WebApr 19, 2024 · Finally, through modulation of pS65-Ub on mitochondria, we demonstrate that Ub hyper-phosphorylation is inhibitory to mitophagy receptor recruitment, indicating that pS65-Ub stoichiometry in vivo is optimized to coordinate PARKIN recruitment via pS65-Ub and mitophagy receptors via unphosphorylated chains.
Phosphorylaiton of ub and parkin in mitophagy
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WebJul 3, 2014 · Parkin, the ubiquitin ligase that is mutated in Parkinson’s disease, regulates the clearance of damaged mitochondria through selective autophagy (mitophagy). Here, Hollville et al. show that Parkin-dependent mitophagy is regulated by members of the Bcl-2 family, which are more commonly known for their ability to regulate apoptotic cell death. WebApr 20, 2024 · Parkin, an E3 ubiquitin (Ub) ligase, mediates the ubiquitination of resident OMM proteins, recruiting Ub-binding autophagic machinery through a feed-forward mechanism to ultimately degrade the organelle via the lysosome ( Heo et al., 2015; Lazarou et al., 2015; Ordureau et al., 2015; Ordureau et al., 2014 ).
WebApr 13, 2024 · Stress-induced mitophagy, a tightly regulated process that targets dysfunctional mitochondria for autophagy-dependent degradation, mainly relies on two proteins, PINK1 and Parkin, which genes are mutated in some forms of familiar Parkinson’s Disease (PD). Upon mitochondrial damage, the protein kinase PINK1 … WebJun 22, 2024 · During induction of mitophagy, Parkin undergoes a series of changes, including binding to pSer65-Ub, recruitment to mitochondria, phosphorylation at its UBL domain (pSer65) by PINK1,...
WebJun 2, 2024 · PINK1 regulates mitochondrial dynamics independent of both parkin and mitophagy. PINK1 regulates mitophagy via recruiting parkin to mitochondria 7, 8, 26, 31, 32. We next asked whether mitophagy was required for PINK1/Drp1 signaling-mediated mitochondrial dynamics. Phosphorylation of Drp1 S616 is not affected in parkin KO cells … WebApr 21, 2014 · PINK1 phosphorylation of Ub to activate Parkin would also explain how PINK1 experimentally located on peroxisomes and lysosomes recruits and activates Parkin ectopically ( Lazarou et al., 2012 ), as PINK1 could phosphorylate Ub present on peroxisomal or lysosomal proteins.
WebSep 12, 2014 · Thus, activation of parkin during mitophagy leads to the generation of K6-, K11-, K48-, and K63-linked Ub chains and the phosphorylation of Ub at S65. To determine the nature of the Ub conjugates on parkin more quantitatively, we carried out in vitro ubiquitination reactions followed by absolute quantification (AQUA) mass spectrometry ...
WebAug 20, 2015 · These phosphorylation events lead to PARKIN recruitment to mitochondria, and activation by an unknown allosteric mechanism. Here we present the crystal structure of Pediculus humanus PARKIN in complex with Ser65-phosphorylated ubiquitin (phosphoUb), revealing the molecular basis for PARKIN recruitment and activation. northgate high school softballWeb73 PINK1- and Parkin-mediated ubiquitination of OMM proteins leads to the recruitment 74 of the Ub-binding mitophagy receptors OPTN and NDP52 (Lazarou et al., 2015), which 75 in turn promote autophagosome initiation (Yamano et al., 2024; Boyle et al., 2024), 76 ultimately leading to degradation of the damaged mitochondria via the autophagy how to say cook dinner in spanishWebApr 19, 2024 · Finally, through modulation of pS65-Ub on mitochondria, we demonstrate that Ub hyper-phosphorylation is inhibitory to mitophagy receptor recruitment, indicating that … northgate hireWebMar 5, 2024 · Phosphatase and tensin homolog (PTEN)-induced kinase (PINK) and Parkin proteins, whose mutations are associated with familial forms of Parkinson’s disease, are two of the best characterized mitophagy players. They accumulate at ER–mitochondria contact sites and modulate organelles crosstalk. how to say convivialitynorthgate high school term dates 2022WebApr 7, 2024 · Activation of Parkin is well established to involve direct phosphorylation by PINK1 and the direct binding of phosphorylated ubiquitin to Parkin, resulting in additional … how to say conventWebRotenone treatment led to not only the activation of p38 but also Parkin inactivation and reactive oxygen species (ROS) overproduction in SN4741 cells. Meanwhile, p38 activation regulated Parkin phosphorylation at serine 131 to disrupt Parkin-mediated mitophagy. Notably, both p38 inhibition and Parkin overexpression decreased ROS levels. how to say cook in asl