USP30: protector of peroxisomes and mitochondria

Riccio, Victoria; McQuibban, G. Angus; Kim, Peter K.

doi:10.1080/23723556.2019.1600350

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…Interestingly, in addition to regulating mitophagy, USP30, the OMM protein, also targets to peroxisomes in a PINK1/Parkin-independent manner 265 . Overexpression of USP30 prevents pexophagy during amino acid starvation, by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2 266 , 267 ( Figure 6 B ). Therefore, an important focus for future studies of USP30 may provide new targets and tools for studying pexophagy in human health and disease.…”

Section: Pexophagy: a Mechanism For Peroxisome Turnover And Homeostasmentioning

confidence: 99%

Selective autophagy of intracellular organelles: Recent research advances

et al. 2021

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Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.

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Section: Pexophagy: a Mechanism For Peroxisome Turnover And Homeostasmentioning

confidence: 99%

Selective autophagy of intracellular organelles: Recent research advances

et al. 2021

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“…USP30, a deubiquitinating enzyme, is crucial in regulating protein stability, presenting another dimension of the molecular interplay in CC. [ 26 ] Our study extended this understanding by linking USP30‐AS1 and USP30 to the activation of the Wnt/β‐catenin signaling pathway, a pathway critical to the diagnosis and prognosis of CC. [ 27 ] We demonstrated that USP30‐AS1 and USP30 can stabilize β‐catenin protein by inhibiting its ubiquitination, further influencing CC progression.…”

Section: Discussionmentioning

confidence: 81%

“…[ 24 ] MiR‐2467‐3p, a microRNA implicated in various cancers including colorectal and nonsmall cell lung cancer, has been identified as a tumor suppressor in CC. [ 25–27 ] Our investigations revealed that USP30‐AS1 modulates USP30 expression by interacting with miR‐2467‐3p. However, intriguingly, suppression of miR‐2467‐3p did not completely revert the effects of USP30‐AS1 knockdown on USP30 expression, suggesting the involvement of additional mediators in this regulatory axis.…”

Section: Discussionmentioning

confidence: 90%

Exosomal lncRNA USP30‐AS1 activates the Wnt/β‐catenin signaling pathway to promote cervical cancer progression via stabilization of β‐catenin by USP30

Chi,

Tang,

Liu

et al. 2024

Biotechnology Journal

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Cervical cancer (CC) remains a major cause of cancer‐related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30‐AS1), in CC tumorigenesis. We analyzed USP30‐AS1 expression using RT‐qPCR and conducted in vitro loss‐of‐function assays, as well as in vivo assays, to evaluate the effects of USP30‐AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull‐down, RNA immunoprecipitation (RIP), and co‐immunoprecipitation (Co‐IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30‐AS1. We discovered that USP30‐AS1 is overexpressed in CC tissues and cells. Silencing USP30‐AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30‐AS1 was found to modulate the expression of ubiquitin‐specific peptidase 30 (USP30) by sponging microRNA‐2467‐3p (miR‐2467‐3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing β‐catenin and activating the Wnt/β‐catenin signaling pathway. These findings suggest that USP30‐AS1 enhances CC cell growth and migration through the miR‐2467‐3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.

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“…Furthermore, hyperubiquitination occurs sequentially at different sites of mitochondria, leading to autophagy machinery and mitophagy. 4,5 Mitophagic biological processes are triggered in response to endogenous mitochondrial damage and persuaded by chemical depolarization. 6−8 Such phenomena are important in mitigating cellular damage in alcohol-induced liver toxicity, drug-induced kidney damage, neurodegeneration, and so forth.…”

Section: Introductionmentioning

confidence: 99%

“…Mitophagy ensures damaged mitochondrial clearance by membrane depolarization, leading to PINK1 adherence to the mitochondrial outer membrane (MOM), thereby phosphorylating ubiquitin and thus activating ubiquitin E3 ligase and Parkin. Furthermore, hyperubiquitination occurs sequentially at different sites of mitochondria, leading to autophagy machinery and mitophagy. , Mitophagic biological processes are triggered in response to endogenous mitochondrial damage and persuaded by chemical depolarization. − Such phenomena are important in mitigating cellular damage in alcohol-induced liver toxicity, drug-induced kidney damage, neurodegeneration, and so forth. , …”

Section: Introductionmentioning

confidence: 99%

Novel Imidazole Phenoxyacetic Acids as Inhibitors of USP30 for Neuroprotection Implication via the Ubiquitin-Rho-110 Fluorometric Assay: Design, Synthesis, and In Silico and Biochemical Assays

Mandal

Kumar

Alam

et al. 2022

ACS Chem. Neurosci.

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USP30, a deubiquitinating enzyme family, forfeits the ubiquitination of E3 ligase and Parkin on the surface of mitochondria. Inhibition of USP30 results in mitophagy and cellular clearance. Herein, by understanding structural requirements, we discovered potential USP30 inhibitors from an imidazole series of ligands via a validated ubiquitin-rhodamine-110 fluorometric assay. A novel catalytic use of the Zn(l-proline)2 complex for the synthesis of tetrasubstituted imidazoles was identified. Among all compounds investigated, 3g and 3f inhibited USP30 at IC50 of 5.12 and 8.43 μM, respectively. The binding mode of compounds at the USP30 binding site was understood by a docking study and interactions with the key amino acids were identified. Compound 3g proved its neuroprotective efficacy by inhibiting apoptosis on SH-SY5Y neuroblastoma cells against dynorphin A (10 μM) treatment. Hence, the present study provides a new protocol to design and develop ligands against USP30, thereby offering a therapeutic strategy under conditions like kidney damage and neurodegenerative disorders including Parkinson’s disease.

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USP30: protector of peroxisomes and mitochondria

Cited by 4 publications

References 10 publications

Selective autophagy of intracellular organelles: Recent research advances

Selective autophagy of intracellular organelles: Recent research advances

Exosomal lncRNA USP30‐AS1 activates the Wnt/β‐catenin signaling pathway to promote cervical cancer progression via stabilization of β‐catenin by USP30

Novel Imidazole Phenoxyacetic Acids as Inhibitors of USP30 for Neuroprotection Implication via the Ubiquitin-Rho-110 Fluorometric Assay: Design, Synthesis, and In Silico and Biochemical Assays

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