Evidence map›Paper›PMID 25621951›Full record

ArticleNature cell biology2015

USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria.

Christian N Cunningham, Joshua M Baughman, Lilian Phu, Joy S Tea, Christine Yu, Mary Coons, Donald S Kirkpatrick, Baris Bingol, Jacob E Corn

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 1 pooled it
15.1field-weighted citation impact, top 1% 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

192 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.

  1. Pooled it
  2. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
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  7. [Deubiquitinase USP30 alleviates brain injury after intracerebral hemorrhage by regulating MFN2 ubiquitination].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. USP25 inhibition ameliorates Parkinson's disease by restoring mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

132 more citing papers are in PubMed but not listed here.

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

9 authors at 4 institutions in 2 countries.

Christian N CunninghamDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Joshua M BaughmanDepartment of Protein Chemistry, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Lilian PhuDepartment of Protein Chemistry, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Joy S TeaDepartment of Neuroscience, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Christine YuDepartment of Structural Biology, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Mary CoonsDepartment of Structural Biology, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Donald S KirkpatrickDepartment of Protein Chemistry, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Baris BingolDepartment of Neuroscience, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
Jacob E CornDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way South San Francisco, California 94080, USA.
PDL BioPharma (United States) · USAntigen Discovery (United States) · USEos Neuroscience (United States) · USInstitute for Structural Research · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple lines of evidence indicate that mitochondrial dysfunction is central to Parkinson's disease. Here we investigate the mechanism by which parkin, an E3 ubiquitin ligase, and USP30, a mitochondrion-localized deubiquitylase, regulate mitophagy. We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. Using mass spectrometry, we show that recombinant USP30 preferentially removes these linkage types from intact ubiquitylated mitochondria and counteracts parkin-mediated ubiquitin chain formation in cells. These results, combined with a series of chimaera and localization studies, afford insights into the mechanism by which a balance of ubiquitylation and deubiquitylation regulates mitochondrial homeostasis, and suggest a general mechanism for organelle autophagy.

Indexed as

HomeostasisCarbonyl Cyanide m-Chlorophenyl HydrazoneCatalytic DomainCell ExtractsGene Knockdown TechniquesGreen Fluorescent ProteinsHEK293 CellsHeLa CellsHumansHydrogen-Ion ConcentrationLysineMass SpectrometryMembrane Potential, MitochondrialMitochondriaMitochondrial ProteinsMitophagyCarbonyl Cyanide m-Chlorophenyl HydrazoneCell ExtractsGreen Fluorescent ProteinsLysineMitochondrial Proteinsparkin proteinThiolester HydrolasesUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUsp30 protein, human

Identifiers

PMID25621951
OpenAlexW2070463829

What OpenQuestion holds

Textmetadata
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.