Evidence map›Paper›PMID 34844982›Full record

ArticleLife science alliance2022

Benchmarking a highly selective USP30 inhibitor for enhancement of mitophagy and pexophagy.

Emma V Rusilowicz-Jones, Francesco G Barone, Fernanda Martins Lopes, Elezabeth Stephen, Heather Mortiboys, Sylvie Urbé, Michael J Clague

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026
    Review
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  5. Article
  6. Article
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  8. Review
  9. Review
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  11. Review
  12. Article
  13. Article
  14. Review
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  16. Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Emma V Rusilowicz-JonesDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Francesco G BaroneDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.ORCID 0000-0003-4382-9313
Fernanda Martins LopesSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Elezabeth StephenSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Heather MortiboysSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.ORCID 0000-0001-6439-0579
Sylvie UrbéDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK urbe@liv.ac.uk.
Michael J ClagueDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK clague@liv.ac.uk.ORCID 0000-0003-3355-9479
University of Liverpool · GBUniversity of Sheffield · GB

Funding

Parkinson's UK F-1301Wellcome Trust
6 · The paper itself

Abstract

The deubiquitylase USP30 is an actionable target considered for treatment of conditions associated with defects in the PINK1-PRKN pathway leading to mitophagy. We provide a detailed cell biological characterization of a benzosulphonamide molecule, compound 39, that has previously been reported to inhibit USP30 in an in vitro enzymatic assay. The current compound offers increased selectivity over previously described inhibitors. It enhances mitophagy and generates a signature response for USP30 inhibition after mitochondrial depolarization. This includes enhancement of TOMM20 and SYNJ2BP ubiquitylation and phosphoubiquitin accumulation, alongside increased mitophagy. In dopaminergic neurons, generated from Parkinson disease patients carrying loss of function PRKN mutations, compound 39 could significantly restore mitophagy to a level approaching control values. USP30 is located on both mitochondria and peroxisomes and has also been linked to the PINK1-independent pexophagy pathway. Using a fluorescence reporter of pexophagy expressed in U2OS cells, we observe increased pexophagy upon application of compound 39 that recapitulates the previously described effect for USP30 depletion. This provides the first pharmacological intervention with a synthetic molecule to enhance peroxisome turnover.

Indexed as

Dose-Response Relationship, DrugHumansMitochondrial ProteinsMitophagyProtease InhibitorsSubstrate SpecificityThiolester HydrolasesUbiquitinationMitochondrial ProteinsProtease InhibitorsThiolester HydrolasesUsp30 protein, human

Identifiers

PMID34844982
PMCPMC8645336
OpenAlexW3214993193

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.