The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
Parkin-catalyzed Ubiquitin-Ester Transfer Is Triggered by PINK1-dependent Phosphorylation
Open accessAbstract
PINK1 and PARKIN are causal genes for autosomal recessive familial Parkinsonism. PINK1 is a mitochondrial Ser/Thr kinase, whereas Parkin functions as an E3 ubiquitin ligase. Under steady-state conditions, Parkin localizes to the cytoplasm where its E3 activity is repressed. A decrease in mitochondrial membrane potential triggers Parkin E3 activity and recruits it to depolarized mitochondria for ubiquitylation of mitochondrial substrates. The molecular basis for how the E3 activity of Parkin is re-established by mitochondrial damage has yet to be determined. Here we provide in vitro biochemical evidence for ubiquitin-thioester formation on Cys-431 of recombinant Parkin. We also report that Parkin forms a ubiquitin-ester following a decrease in mitochondrial membrane potential in cells, and that this event is essential for substrate ubiquitylation. Importantly, the Parkin RING2 domain acts as a transthiolation or acyl-transferring domain rather than an E2-recruiting domain. Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. A phosphorylation-deficient mutation completely inhibited formation of the Parkin ubiquitin-ester intermediate, whereas phosphorylation mimics, such as Ser to Glu substitution, enabled partial formation of the intermediate irrespective of Ser-65 phosphorylation. We propose that PINK1-dependent phosphorylation of Parkin leads to the ubiquitin-ester transfer reaction of the RING2 domain, and that this is an essential step in Parkin activation. Background: Parkin is a ubiquitin ligase activated by a decrease in the mitochondrial membrane potential (ΔΨm). However, details regarding its mechanism remain limited. Results: PINK1-dependent phosphorylation of Parkin at Ser-65 following dissipation of ΔΨm triggers ubiquitin-ester transfer by the RING2 domain of Parkin to Cys-431. Conclusion: Parkin catalyzes trans- (ubiquitin-thioester)ification upon PINK1-dependent phosphorylation. Significance: The molecular process of Parkin-catalyzed ubiquitylation has been determined.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both events are required for the activation of the pathway.”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Upon mitochondrial depolarization, PINK1 stabilizes on the outer mitochondrial membrane, where it phosphorylates ubiquitin (Ub) and PRKN at Ser65 [5–10].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [10]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Narendra, D. P., Jin, S. M., Tanaka, A., Suen, D.-F., Gautier, C. A., Shen, J., Cookson, M. R., & Youle, R. J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000298 · Cited by 2,944
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835
RING Domain E3 Ubiquitin Ligases
Deshaies, R. J., & Joazeiro, C. A. P. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.101807.093809 · Cited by 2,679
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024
Self-citationMatsuda, N., Sato, S., Shiba, K., Okatsu, K., Saisho, K., Gautier, C. A., Sou, Y.-S., Saiki, S., Kawajiri, S., Sato, F., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200910140 · Cited by 1,969
Self-citationDrosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788
A tissue-specific atlas of mouse protein phosphorylation and expression
Huttlin, E. L., Jedrychowski, M. P., Elias, J. E., Goswami, T., Rad, R., Beausoleil, S. A., Villén, J., Haas, W., Sowa, M. E., & Gygi, S. P. (2010) · Cell · doi:10.1016/j.cell.2010.12.001 · Cited by 1,778
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–209 of 209
Structural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complexPreprint
Okatsu, K., Yamamoto, H., Okamoto, A., Goto, S., Nishimoto, Y., Sugita, Y., Noda, T., & Fukai, S. (2026) · eLife · doi:10.7554/elife.110255.1
Self-citationStructural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complexPreprint
Okatsu, K., Yamamoto, H., Okamoto, A., Goto, S., Nishimoto, Y., Sugita, Y., Noda, T., & Fukai, S. (2026) · eLife · doi:10.7554/elife.110255
Self-citationKhalil, B. (2016) · theses.fr (ABES) · doi:10.70675/4446111fz4182z4737zae76z7f117887a893
Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson’s Disease
Shen, Z., Ma, L., & Mellick, G. D. (2026) · Biomedicines · doi:10.3390/biomedicines14051162
Robust and sensitive ELISA detection of total and activated PRKN
Watzlawik, J. O., Bustillos, B. A., Martinez, C. R., Dickson, D. W., Wszołek, Z. K., Ross, O. A., Springer, W., & Fiesel, F. C. (2026) · Autophagy · doi:10.1080/15548627.2026.2694658
P INK1/PARKIN mitophagy: a potential regulator of mitochondrial homeostasis in functional dyspepsia
Li, P., Wang, Y., Dong, Y., Zhang, X., & Shang, K. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1881965
Revisiting Inherited Metabolic Diseases ( IMDs ) Through the Lens of Selective Autophagy
Maddaluno, M., Cinque, L., Cetrangolo, V., & Leonibus, C. D. (2026) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.70259
Molecular Mechanisms of Mitochondrial Transport in Neurons
Babić, M. (2015) · UA Campus Repository (The University of Arizona)
Metadata
- Authors
- Iguchi, M., Kujuro, Y., Okatsu, K., Koyano, F., Kosako, H., Kimura, M., Suzuki, N., Uchiyama, S., Tanaka, K., & Matsuda, N.
- Affiliations
- Tokyo Metropolitan Institute of Medical Science (JP)
- Keio University (JP)
- Tokushima University (JP)
- Tokyo Women's Medical University (JP)
- Corresponding author
- Tanaka, Keiji
- Matsuda, Noriyuki
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 288
- Issue
- 30
- Pages
- 22019-22032
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3724655
- OpenAlex
- W2015758704
- Cited by
- 209
- References
- 75
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 13 · 2021: 19 · 2020: 16 · 2019: 12 · 2018: 13 · 2017: 8 · 2016: 18 · 2015: 36 · 2014: 25 · 2013: 5
- FWCI
- 17.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion, cc-by)
- Funders
- Japan Society for the Promotion of Science (23570231, 25860721)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Parkin, PINK1, mitochondrial membrane potential, mitochondrial depolarization, familial parkinsonism
- MeSH terms
- PTEN-Induced Putative Kinase, Animals, Binding Sites, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Cells, Cultured, Cysteine, Embryo, Mammalian, Esters, Fibroblasts, HeLa Cells, Humans, Models, Biological, Phosphorylation, Protein Kinases, Serine, Substrate Specificity, Immunoblotting, Mice, Knockout, Ubiquitin, Ubiquitin-Protein Ligases, Mice, Membrane Potential, Mitochondrial, Ubiquitination, Biocatalysis, HEK293 Cells, Proton Ionophores
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
