The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Open accessAbstract
Although serum from patients with Parkinson's disease contains elevated levels of numerous pro-inflammatory cytokines including IL-6, TNF, IL-1β, and IFNγ, whether inflammation contributes to or is a consequence of neuronal loss remains unknown 1. Mutations in parkin, an E3 ubiquitin ligase, and PINK1, a ubiquitin kinase, cause early onset Parkinson's disease 2,3. Both PINK1 and parkin function within the same biochemical pathway and remove damaged mitochondria from cells in culture and in animal models via mitophagy, a selective form of autophagy 4. The in vivo role of mitophagy, however, is unclear, partly because mice that lack either PINK1 or parkin have no substantial Parkinson's-disease-relevant phenotypes 5-7. Mitochondrial stress can lead to the release of damage-associated molecular patterns (DAMPs) that can activate innate immunity 8-12, suggesting that mitophagy may mitigate inflammation. Here we report a strong inflammatory phenotype in both Prkn-/- and Pink1-/- mice following exhaustive exercise and in Prkn-/-;mutator mice, which accumulate mutations in mitochondrial DNA (mtDNA)13,14. Inflammation resulting from either exhaustive exercise or mtDNA mutation is completely rescued by concurrent loss of STING, a central regulator of the type I interferon response to cytosolic DNA 15,16. The loss of dopaminergic neurons from the substantia nigra pars compacta and the motor defect observed in aged Prkn-/-;mutator mice are also rescued by loss of STING, suggesting that inflammation facilitates this phenotype. Humans with mono- and biallelic PRKN mutations also display elevated cytokines. These results support a role for PINK1- and parkin-mediated mitophagy in restraining innate immunity.
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
“Multiple studies have revealed that loss of PRKN and PINK1 dysregulated mitophagy and increased mitochondria stress, leading to mito-inflammation,267 which was recently suggested to be involved in PD pathology in PINK1 and PRKN deficient mice.268”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [268]
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
“Knockout of STING reverses motor deficit and neuron loss in aged PRKN knockout PD mouse model.268”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [268]
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
“peripheral dysregulation of IFN production is linked with the pathogenesis of CNS neurodegenerative conditions.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [84]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Together with previous studies in models of Alzheimer’s disease53, Parkinson’s disease54,55, amyotrophic lateral sclerosis and frontotemporal dementia56, and Nieman–Pick’s disease57, our study reveals notable convergence on cGAS–STING signalling in chronic neurodegenerative conditions.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [54]
In the citing paper
“Genetic and pharmacological restorations of autophagic/mitophagic clearance in animal models of these diseases ameliorate disease-defining pathologies and behavioral deficits (Fang et al., 2019; Ravikumar et al., 2004; Sliter et al., 2018).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Sliter et al., 2018
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
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
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
Skyline: an open source document editor for creating and analyzing targeted proteomics experiments
MacLean, B., Tomazela, D. M., Shulman, N., Chambers, M., Finney, G. L., Frewen, B., Kern, R., Tabb, D. L., Liebler, D. C., & MacCoss, M. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq054 · Cited by 4,697
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310
Self-citationMitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975
Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants
Greene, J. C., Whitworth, A. J., Kuo, I., Andrews, L. A., Feany, M. B., & Pallanck, L. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0737556100 · Cited by 1,203
NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.057 · Cited by 1,197
Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production
White, M. J., McArthur, K., Metcalf, D., Lane, R. M., Cambier, J. C., Herold, M. J., van Delft, M. F., Bedoui, S., Lessene, G., Ritchie, M. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.036 · Cited by 983
Parkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons
Goldberg, M. S., Fleming, S. M., Palacino, J. J., Cepeda, C., Lam, H. A., Bhatnagar, A., Meloni, E. G., Wu, N., Ackerson, L. C., Klapstein, G. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308947200 · Cited by 913
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux, A., Jackson, R., Harman, C. C. D., Li, T., West, A. P., de Zoete, M. R., Wu, Y., Yordy, B., Lakhani, S. A., Kuan, C.-Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.037 · Cited by 847
Biochemical markers of muscular damage
Brancaccio, P., Lippi, G., & Maffulli, N. (2010) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2010.179 · Cited by 844
Meta‐analysis of early nonmotor features and risk factors for Parkinson disease
Noyce, A. J., Bestwick, J. P., Silveira‐Moriyama, L., Hawkes, C. H., Giovannoni, G., Lees, A. J., & Schrag, A. E. (2012) · Annals of Neurology · doi:10.1002/ana.23687 · Cited by 834
Sun, N., Yun, J., Liu, J., Malide, D. A., Liu, C., Rovira, I. I., Holmström, K. M., Fergusson, M. M., Yoo, Y. H., Combs, C. A., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.009 · Cited by 718
Self-citationActivation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases
Gao, D., Li, T., Li, X.-D., Chen, X., Li, Q., Wight‐Carter, M., & Chen, Z. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516465112 · Cited by 685
Self-citationParkinson’s Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation
Matheoud, D., Sugiura, A., Bellemare-Pelletier, A., Laplante, A., Rondeau, C., Chemali, M., Fazel, A., Bergeron, J. J., Trudeau, L.-E., Burelle, Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.039 · Cited by 582
Impaired dopamine release and synaptic plasticity in the striatum of PINK1 -deficient mice
Kitada, T., Pisani, A., Porter, D. R., Yamaguchi, H., Tscherter, A., Martella, G., Bonsi, P., Zhang, C., Pothos, E. N., & Shen, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702717104 · Cited by 550
Sauer, J., Troha, K., von Moltke, J., Monroe, K. M., Rae, C. S., Brubaker, S. W., Hyodo, M., Hayakawa, Y., Woodward, J. J., Portnoy, D. A., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00999-10 · Cited by 528
PINK1 mutations are associated with sporadic early‐onset parkinsonism
Valente, E. M., Salvi, S., Ialongo, T., Marongiu, R., Elia, A. E., Caputo, V., Romito, L. M., Albanese, A., Dallapiccola, B., & Bentivoglio, A. R. (2004) · Annals of Neurology · doi:10.1002/ana.20256 · Cited by 506
Parkin-deficient mice are not a robust model of parkinsonism
Perez, F. A., & Palmiter, R. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409598102 · Cited by 477
Matsuura, K., Kabuto, H., Makino, H., & Ogawa, N. (1997) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(96)02211-x · Cited by 434
Herzig, M. C., Kolly, C., Persohn, E., Theil, D. J., Schweizer, T., Hafner, T., Stemmelen, C., Troxler, T. J., Schmid, P., Danner, S., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr348 · Cited by 371
A fluorescence-based imaging method to measure in vitro and in vivo mitophagy using mt-Keima
Sun, N., Malide, D. A., Liu, J., Rovira, I. I., Combs, C. A., & Finkel, T. (2017) · Nature Protocols · doi:10.1038/nprot.2017.060 · Cited by 350
Self-citationA simple quantitative bradykinesia test in MPTP-treated mice.
Ogawa, N., Hirose, Y., Ohara, S., Ono, T., & Watanabe, Y. (1985) · PubMed · Cited by 334
Pickrell, A. M., Huang, C.-H., Kennedy, S. R., Ordureau, A., Sideris, D. P., Hoekstra, J. G., Harper, J. W., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.034 · Cited by 327
Self-citationSheehan, K. C. F., Lai, K. S., Dunn, G. P., Bruce, A. T., Diamond, M. S., Heutel, J. D., Dungo-Arthur, C., Carrero, J. A., White, J. M., Hertzog, P. J., et al. (2006) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.26.804 · Cited by 260
Inflammation is genetically implicated in Parkinson’s disease
Dzamko, N., Geczy, C. L., & Halliday, G. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.028 · Cited by 222
Greene, J. C., Whitworth, A. J., Andrews, L. A., Parker, T. J., & Pallanck, L. J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi074 · Cited by 194
Improved Quantitative Mass Spectrometry Methods for Characterizing Complex Ubiquitin Signals
Phu, L., Izrael-Tomasevic, A., Matsumoto, M. L., Bustos, D. J., Dynek, J. N., Fedorova, A. V., Bakalarski, C. E., Arnott, D. P., Deshayes, K., Dixit, V. M., et al. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.003756 · Cited by 144
Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress
Guzmán, J. N., Ilijić, E., Yang, B., Sánchez-Padilla, J., Wokosin, D. L., Galtieri, D. J., Kondapalli, J., Schumacker, P. T., & Surmeier, D. J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95898 · Cited by 137
Hørder, M., Elser, R. C., Gerhardt, W., Mathieu, M., & Sampson, E. J. (1991) · PubMed · Cited by 71
Immunology, Autoimmunity, and Autoantibodies in Parkinson’s Disease
Benkler, M., Agmon‐Levin, N., Hassin‐Baer, S., Cohen, O. S., Ortega‐Hernandez, O., Levy, A., Moscavitch, S.-D., Szyper‐Kravitz, M., Damianovich, M., Blank, M., et al. (2011) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8242-y · Cited by 47
Accurate quantitation of circulating cell-free mitochondrial DNA in plasma by droplet digital PCR
Ye, W., Tang, X., Liu, C., Wen, C., Li, W., & Lyu, J. (2017) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-017-0217-x · Cited by 42
Cohort Profile: A population-based cohort to study non-motor symptoms in parkinsonism (EPIPARK)
Kasten, M., Hagenah, J. M., Gräf, J., Lorwin, A., Vollstedt, E., Peters, E., Katalinic, A., Raspe, H. H., & Klein, C. (2012) · International Journal of Epidemiology · doi:10.1093/ije/dys202 · Cited by 39
Self-citation
Cited by
Sorted by citations
Bloem, B. R., Okun, M. S., & Klein, C. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00218-x · Cited by 3,920
Self-citationAgeing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
Biological Functions of Autophagy Genes: A Disease Perspective
Levine, B., & Kroemer, G. (2019) · Cell · doi:10.1016/j.cell.2018.09.048 · Cited by 2,832
The molecular machinery of regulated cell death
Tang, D., Kang, R., Berghe, T. V., Vandenabeele, P., & Kroemer, G. (2019) · Cell Research · doi:10.1038/s41422-019-0164-5 · Cited by 2,675
Mitochondria as multifaceted regulators of cell death
Bock, F. J., & Tait, S. W. G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0173-8 · Cited by 2,531
Metadata
- Authors
- Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., Cai, H., Borsche, M., Klein, C., & Youle, R. J.
- Affiliations
- National Institutes of Health (US)
- University of Lübeck (DE)
- Corresponding author
- Youle, Richard J.
- ORCID
- Venue
- Nature
- Published
- 2018-08-22
- Volume
- 561
- Issue
- 7722
- Pages
- 258-262
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7362342
- OpenAlex
- W2887997888
- Cited by
- 1,287
- References
- 39
- Citations by year
- 2026: 68 · 2025: 177 · 2024: 190 · 2023: 185 · 2022: 180 · 2021: 197 · 2020: 157 · 2019: 115 · 2018: 16
- FWCI
- 82.18
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (DFG FOR2488)
- National Institute of Neurological Disorders and Stroke (Z01NS002859, ZIANS002859)
- National Institute of Environmental Health Sciences (1ZIAES10328601, ZIAES103286)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- Parkin, PINK1, STING, mitophagy, Parkinson's disease, neuroinflammation, mitochondrial DNA mutations, exhaustive exercise, innate immunity, dopaminergic neurons, substantia nigra pars compacta, motor impairment, type I interferon response, cytosolic DNA, E3 ubiquitin ligase
- MeSH terms
- Alarmins, STING Protein, PTEN-Induced Putative Kinase, Animals, DNA, Mitochondrial, Humans, Immunity, Innate, Inflammation, Membrane Proteins, Mice, Inbred C57BL, Parkinson Disease, Physical Conditioning, Animal, Protein Kinases, Stress, Physiological, Ubiquitin-Protein Ligases, Mice, Receptor, Interferon alpha-beta, Mitophagy
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
