IndraLab

Statements

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"USP8 Down-Regulation Enhances Basal Mitophagy in S2R+ cells."
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"Thus, important prerequisites for compound optimization and drug development exist for USP8 and can be readily exploited in aged-associated neurodegenerative disease models.In summary, in this work we show that we can enhance autophagy and mitophagy by down-regulating USP8, a DUB that is upregulated in age-related neurodegenerative conditions [19,42]."
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"These results support the hypothesis that basal mitophagy is induced by USP8 down-regulation and that the mitophagic effect of USP8 down-regulation under basal conditions is Parkin independent."
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"By contrast, USP8 can positively regulate mitophagy through specifically eliminating K6 ubiquitin chain on Parkin."
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"Unlike other DUBs, however, USP8 positively regulates mitophagy by removing K6-linked ubiquitin chains from Parkin [155]."
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"In summary, high expression of USP8 may promote the occurrence of mitophagy through the TGF‐β signaling pathway, thereby reducing the number of CD4 naïve T cells, which needs further confirmation.CDKN2B (Cyclin‐dependent kinase 4 inhibitor B) is a potent inhibitor of various tumors, which can inhibit the TGF‐β‐mediated cell cycle, and was also enriched in the TGF‐β signaling pathway of the hub genes."
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"Parkin is in turn regulated by several DUBs; USP8 promotes Parkin activity and mitophagy by removing the K6-linked ubiquitin chains, which prevent Parkin’s interaction with the phosphorylated ubiquitin and PINK1 [157], while USP15 and USP30 antagonize Parkin by removing ubiquitin chains from mitochondria, preventing the binding of mitophagy receptors [158,159]."
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"USP8 Down-Regulation Promotes Parkin-Independent Mitophagy in the Drosophila Brain and in Human Neurons."
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"Clec16-RNF41-USP8 complex led to regulated mitophagy and normal insulin secretion, while disruption of the complex by stressors induced aberrant mitophagy and impaired β-cell function [60], [61]."
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"These approaches allowed identifying a mitophagic effect of USP8 down-regulation, which was clearly detectable in vivo in the fly brain and also in neurons of human origin.Interestingly, USP8 down-regulation promoted basal mitophagy in a Parkin-independent fashion (Figure 2D,E), whereas it inhibited Parkin mitochondrial translocation and mitophagy under stress condition (Supplementary Figure S3)."
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"Conversely, USP8 specifically cleaves Lys6-linked ubiquitin conjugates from Parkin and activates Parkin-dependent mitophagy [24]."
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"We found that USP8 down-regulation enhances autophagy and mitophagy in flies and in neurons of human origin, providing a mechanistic explanation for the protective effect of USP8 reduction observed in several models of neurodegeneration."
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"USP8 Down-Regulation Induces Mitophagy in Flies."
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