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USP30 inhibits pexophagy. 13 / 13
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"Our laboratory has shown that depletion of USP30 enhances basal levels of pexophagy in mammalian cells, whilst others have shown that USP30 overexpression can counteract E3 activity of PEX2 during sta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The deubiquitinating enzyme ubiquitin-specific protease 30 (USP30) can inhibit pexophagy by antagonizing PEX2, thus maintaining the balance of the number of peroxisomes in cells [63]."
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"Interestingly, USP30 artificially targeted to peroxisomes was shown to reduce pexophagy (Cunningham et al., 2015)."
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"Interestingly, it has been recently reported that USP30, an integral protein of the outer mitochondrial membrane, can also localise to peroxisomes to negatively regulate pexophagy (Marcassa et al, 2018)."
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"We found that USP30-Flag C77S and PMP34-USP30 C77S were unable to prevent peroxisome loss (Fig. 2, B and E), suggesting that USP30’s deubiquitination activity is required to prevent starvation-induced peroxisome loss.Finally, to test whether USP30 prevents pexophagy, we examined the targeting of peroxisomes to lysosomes using a pH-sensing autophagy assay, the red-green (RG) assay (Deosaran et al., 2013)."
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"To test whether USP30 can prevent pexophagy in this background we overexpressed USP30 in a PEX1 G843D PBD cell line and found that it can rescue the loss of peroxisomes, suggesting a potential therapeutic approach in combatting this disease.During the revision of our manuscript, a study was published by Sylvie Urbé’s group demonstrating that endogenous USP30 localizes to the peroxisome where it regulates basal pexophagy."
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"We propose that if USP30 prevents pexophagy by removing ubiquitin on peroxisomes, then overexpressing USP30 should prevent NBR1 recruitment to peroxisomes during starvation."
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"We presumed that USP30 inhibition by CMPD-39 must be promoting pexophagy via an alternative ubiquitin-dependent pathway."
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"This further supports the hypothesis that USP30 prevents pexophagy by removing ubiquitin on peroxisomes."
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"USP30 knockdown enhances pexophagy in FAF2-deficient cells."
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"Similarly, forced USP30 overexpression suppresses pexophagy and prevents peroxisome loss in the same PBD cell model [73]."
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"USP30 has been proposed to counter the action of the peroxisomal E3-ligase PEX2 and suppress pexophagy in response to amino acid starvation (23)."
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"The depletion of USP30 increases both pexophagy and mitophagy ."
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