Phosphorylaiton of ub and parkin in mitophagy

Author: haac

August undefined, 2024

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 … WebFig. 1. UB-replacement reveals roles of p-S65 in UB and PARKIN in PINK1-dependent ubiquitylation of outer mitochondrial membrane proteins. ( Aand B) Effect of …

Structural mechanisms of mitochondrial quality control mediated …

WebNov 9, 2024 · Specific phosphorylation of either Ub or Ubl leads to PARKIN activation; concomitant phosphorylation, however, leads to enhanced PARKIN activation [91, 92, 94]. Binding of pUb to PARKIN ’ s Ubl domain is essential for remodelling of and exposure of RING1 to the binding of the Ub containing E2s and is in line with previous computational ... WebApr 12, 2024 · The parkin∼Ub intermediate itself is short-lived, and the ubiquitin is rapidly transferred to lysine residues of nearby substrates, including ubiquitin chains and parkin itself (Figure 3 C). The large distance between the E2 binding and catalytic sites in the inactive conformation led to the suggestion that parkin may act as a dimer ( Kumar ... philip gabriel property

Parkin drives pS65-Ub turnover independently of canonical …

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. 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. WebNov 30, 2016 · Fig. 2. PINK1/Parkin-directed mitochondria quality control. Shown is a cartoon of the PINK1/Parkin pathway(s). (A) In healthy mitochondria, PINK1 is imported and it undergoes cleavage by the mitochondrial proteases MPP and PARL. N-terminally cleaved PINK1 is then subsequently degraded by the Ub/proteasome system. Parkin remains … philip fusz buch

Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent ... - eLife

Dynamics of PARKIN-Dependent Mitochondrial …

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 … 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 ... philip furrWebApr 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 ). philip fuson

"WebOct 12, 2024 · Here we show that like Ub, NEDD8 is phosphorylated by PINK1 at S65 and that pNEDD8 stimulates PINK1-mediated Parkin phosphorylation and in addition acts as … " - Phosphorylaiton of ub and parkin in mitophagy

Phosphorylaiton of ub and parkin in mitophagy

Synthesis and delivery of a stable phosphorylated ubiquitin probe …

WebApr 6, 2015 · UB chain assembly on mitochondria, but not primary ubiquitylation or PARKIN S65 phosphorylation, is reduced in UB S65A -replacement cells. ( A) Cells in which … WebApr 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 …

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Webenzymes (DUBs) have been reported to regulate mitophagy. The formation of p-Ub or poly-Ub chains is consistently re-versed by deubiquitinases, such as USP30 and USP35, which reverse mitophagy by removing Ub chains generated by Par-kin on the OMM (Bingol et al., 2014; Wang et al., 2015). Al-though Parkin is a crucial regulator of mitophagy ... 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,...

WebApr 1, 2024 · Interestingly, PINK1 may also generate p-Ub and recruit NDP52/OPTN independently of Parkin to drive low-level mitophagy, implying the involvement of additional ubiquitin E3 ligases [21 •]. Until recently, it was widely assumed that the ATG-conjugation machinery is crucial for autophagosome biogenesis and cargo incorporation. WebClearance of damaged mitochondria, termed mitophagy, 13 is triggered by ubiquitin (Ub) phosphorylation at serine 65 (pUb) by PTEN-induced kinase 1 (PINK1). 14 PINK1 …

WebJun 22, 2024 · Mitophagy is an important type of selective autophagy for specific elimination of damaged mitochondria. PTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1-Parkin-mediated mitophagy. Phosphatase and tensin homolog (PTEN)-long (PTEN-L) is a newly … WebPTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1-Parkin-mediated mitophagy. Phosphatase and …

WebNov 25, 2024 · Ub-dependent mitophagy usually refers to Pink1-Parkin-mediated mitophagy. Upon mitochondrial depolarization, full-length Pink1 accumulates on the OMM and recruits Parkin to the mitochondrial surface. Pink1 triggers Parkin E3 ligase activity through a circuit of modifications including phosphorylation of both Parkin and ubiquitin.

Web73 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 truewall series 3800WebMay 13, 2024 · Parkin has a high affinity to phosphorylated Ub (pSer65-Ub), which recruits Parkin from cytosol to mitochondria . Several other factors, such as mitofusin 2 (MFN2), … philip fullerton northern marineWebUbiquitin chains assembled by PARKIN on the mitochondrial outer membrane recruit autophagy cargo receptors in complexes with TBK1 protein kinase. While TBK1 is known … true warrior initiativeWebDec 19, 2015 · Hence, determinewhether phosphorylation NIXalso plays importantrole determiningwhether NIX induceautophagy celldeath. ... Parkin-deﬁcient mice have reduced mitophagy accumulatedysfunctional mitochondria after infarction,which leads increasedremodelling reducedsurvival (Kubli et al., 2013). addition,Hoshino et al. recently … true walshWebApr 8, 2024 · Mitophagy failure and mitochondrial dysfunction in iPSC-derived cortical neurons obtained from some cell mines and fluids of patients categorized by reduced levels of Parkin and ATG5, which induced an increase in PINK1, LC3, P-S65-Ub, and TOMMO20 in the mitochondria cavity, thus reducing the macroautophagy degradation. truewall series 4400WebRotenone 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. philip gale upholsteryWeb(10–15, 17) and provide further insight into how phosphorylation of both UB and PARKIN promotes a “feed-forward” mechanism controlling mitochondrial ubiquitylation and mitophagy. Results and Discussion S65D/E Does Not Mimic S65 Phosphorylation in UB or PARKIN. Previous efforts to define roles of phosphorylation of UB S65 in mam- philip fulton attorney