Evidence map›Paper›PMID 34767452›Full record

ArticleScience advances2021

Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1.

Odetta Antico, Alban Ordureau, Michael Stevens, Francois Singh, Raja S Nirujogi, Marek Gierlinski, Erica Barini, Mollie L Rickwood, Alan Prescott, Rachel Toth and 3 more

Abstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
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

46 citing papers in PubMed.

  1. Review
  2. Mass spectrometry proteomics for studying mitostasis.Protein science : a publication of the Protein Society · 2026
    Review
  3. Review
  4. Phospho-ubiquitin: rewriting the ubiquitin code.Molecular neurodegeneration · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025
    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

13 authors.

Odetta AnticoMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-7325-3303
Alban OrdureauDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4924-8520
Michael StevensMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0001-8105-6302
Francois SinghMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-1696-9815
Raja S NirujogiMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Marek GierlinskiData Analysis Group, Division of Computational Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0001-9149-3514
Erica BariniMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-3093-4053
Mollie L RickwoodMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-3715-8915
Alan PrescottDundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-0747-7317
Rachel TothMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0002-1337-0612
Ian G GanleyMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0003-1481-9407
J Wade HarperDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6944-7236
Miratul M K MuqitMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.ORCID 0000-0001-9733-2404

Funding

Regulation of PINK1 and PARKIN-Dependent MitophagyR01NS083524 · NINDS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W · 2020 to 2024
$2.2M
Medical Research Council MC_UU_00018/2NINDS NIH HHS R01 NS083524
6 · The paper itself

Abstract

How activation of PINK1 and Parkin leads to elimination of damaged mitochondria by mitophagy is largely based on cell lines with few studies in neurons. Here, we have undertaken proteomic analysis of mitochondria from mouse neurons to identify ubiquitylated substrates of endogenous Parkin. Comparative analysis with human iNeuron datasets revealed a subset of 49 PINK1 activation–dependent diGLY sites in 22 proteins conserved across mouse and human systems. We use reconstitution assays to demonstrate direct ubiquitylation by Parkin in vitro. We also identified a subset of cytoplasmic proteins recruited to mitochondria that undergo PINK1 and Parkin independent ubiquitylation, indicating the presence of alternate ubiquitin E3 ligase pathways that are activated by mitochondrial depolarization in neurons. Last, we have developed an online resource to search for ubiquitin sites and enzymes in mitochondria of neurons, MitoNUb. These findings will aid future studies to understand Parkin activation in neuronal subtypes.

Identifiers

PMID34767452
PMCPMC8589319

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Registered trials

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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.