Evidence map›Paper›PMID 29166608›Full record

ArticleCell reports2017

S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson's Disease Models.

Chang-Ki Oh, Abdullah Sultan, Joseph Platzer, Nima Dolatabadi, Frank Soldner, Daniel B McClatchy, Jolene K Diedrich, John R Yates, Rajesh Ambasudhan, Tomohiro Nakamura and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 2% 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

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

  1. Rethinking 'rare'Journal of Parkinson's disease · 2025
    Pooled it
  2. Review
  3. Review
  4. Dilating the aging clock with light.Innovation (Cambridge (Mass.)) · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Article
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  11. Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
  17. Review
  18. Stem Cell-Based Approaches in Parkinson's Disease Research.International journal of stem cells · 2025
    Review
  19. Review
  20. Review

30 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

12 authors at 4 institutions in 1 country.

Chang-Ki OhDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Abdullah SultanNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Joseph PlatzerNeuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Nima DolatabadiDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Frank SoldnerWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Daniel B McClatchyDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jolene K DiedrichDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
John R YatesDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rajesh AmbasudhanNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Tomohiro NakamuraDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: tnakamura@scripps.edu.
Rudolf JaenischWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Stuart A LiptonDepartments of Molecular Medicine and Neuroscience and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA. Electronic address: slipton@scripps.edu.
Scripps Research Institute · USDiscovery Institute · USSanford Burnham Prebys Medical Discovery Institute · USWhitehead Institute for Biomedical Research · US

Funding

TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
GENOMIC IMPRINTING AND THE CLONING OF MICER37CA084198 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2000 to 2008
$9.2M
Project 4: A Developmental Perspective to Nitrosative/Oxidative SusceptibilityP01ES016738 · NIEHS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI GU, ZEZONG · 2008 to 2012
$8.5M
In Vitro Reprogramming of Somatic Cells into Pluripotent ES-like CellsR37HD045022 · NICHD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2009 to 2017
$7.5M
Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0M
An iPSC based platform for functionally assessing genetic and environmental riskR01NS088538 · NINDS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, MYERS, RICHARD H · 2014 to 2018
$5.0M
Project-002P30NS076411 · NINDS · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI LIPTON, STUART A · 2011 to 2016
$4.5M
Dynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1M
S-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3M
Modeling Parkinson's Disease with Isogenic hiPSC-Derived Dopaminergic NeuronsR01NS086890 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2014 to 2018
$2.1M
NCI NIH HHS R37 CA084198NIA NIH HHS R01 AG056259NIA NIH HHS RF1 AG057409NICHD NIH HHS R37 HD045022NIDA NIH HHS DP1 DA041722NIEHS NIH HHS P01 ES016738NIGMS NIH HHS P41 GM103533NINDS NIH HHS P30 NS076411NINDS NIH HHS R01 NS086890NINDS NIH HHS R01 NS088538
6 · The paper itself

Abstract

Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases Parkin translocation to mitochondrial membranes, disrupting mitophagy in cell lines and human-iPSC-derived neurons. We find levels of SNO-PINK1 in brains of α-synuclein transgenic PD mice similar to those in cell-based models, indicating the pathophysiological relevance of our findings. Importantly, SNO-PINK1-mediated deficits in mitophagy contribute to neuronal cell death. These results reveal a direct molecular link between nitrosative stress, SNO-PINK1 formation, and mitophagic dysfunction that contributes to the pathogenesis of PD.

Indexed as

AnimalsHumansInduced Pluripotent Stem CellsMiceMitochondriaMitophagyMutationNeuronsParkinson DiseaseProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein Ligasesparkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein LigasesmitophagyPARK2PARK6ParkinParkinson’s diseasePINK1S-nitrosylation

Identifiers

PMID29166608
PMCPMC5705204
OpenAlexW2769796214

What OpenQuestion holds

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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.