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Cited by 154Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingMitochondrial Function and Pathology

PINK1 function in health and disease

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Deas, Emma, Plun‐Favreau, Helene, Wood, Nicholas W.·2009·EMBO Molecular Medicine
DOI 10.1002/emmm.200900024PMC PMC3378127
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Abstract

The role of mitochondria in sporadic Parkinson's disease (PD) has been debated for a little over 20 years since the description of complex I deficiency in the substantia nigra pars compacta (SNpc) of PD patients. However, the identification of recessive pathogenic mutations in the pink1 gene in familial PD cases firmly re-ignited interest in the pathophysiology of mitochondria in PD. PINK1 is a putative mitochondrial serine/threonine kinase, which protects cells against oxidative stress induced apoptosis. The mechanism by which this is achieved and the effect of the pathogenic mutations has been an area of intensive research over the past five years. Significant progress has been made and, in this review, we summarize the physiological roles that have been assigned to PINK1 and the potential mechanisms behind pathogenesis.

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  • Both PINK1 and Parkin have neuroprotective roles against various insults, such as oxidative stress and PD-relevant toxins.

    “Beyond their roles in mitophagy, mounting evidence suggested that both PINK1 and Parkin have neuroprotective roles against various insults, such as oxidative stress and PD-relevant toxins, although the underlying mechanisms still remain elusive [22, 23].”

    From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [23]

    The section “PINK1 protects cells against oxidative stress-induced apoptosis” reports that PINK1 protects against oxidative-stress-induced death and chemical insults including MPTP. The paper discusses Parkin’s role in the PINK1 pathway, but the passages found do not establish that Parkin protects neurons against oxidative stress or PD-relevant toxins. Thus the claim is supported for PINK1, not for both proteins. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • PINK1 plays crucial roles in mitochondria trafficking, spine morphogenesis, and vulnerability to excitotoxicity in neurons.

    “PINK1 also plays crucial roles in mitochondria trafficking, spine morphogenesis, and vulnerability to excitotoxicity in neurons [23].”

    From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [23]

    The “PINK1 and mitochondrial trafficking” section links PINK1 to a transport complex relevant to neurons. The “PINK1 in calcium signalling” section discusses susceptibility of PINK1-deficient dopaminergic neurons to cell death, but does not identify excitotoxicity as the cause. The passages do not support a role in spine morphogenesis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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References 89 · Cited by 154

Research works printed but not linked: 76

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Authors
Deas, E., Plun‐Favreau, H., & Wood, N. W.
Affiliations
National Hospital for Neurology and Neurosurgery (GB)
Corresponding author
Wood, Nicholas W.
ORCID
Wood, Nicholas W.
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2009-06-01
Volume
1
Issue
3
Pages
152-165
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.1002/emmm.200900024
PMC
PMC3378127
OpenAlex
W2114452773
Cited by
154
References
89
Citations by year
2026: 4 · 2025: 14 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 17
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
PINK1, Parkinson's disease, mitochondria, oxidative stress, apoptosis, pathogenic variants, complex I deficiency, substantia nigra pars compacta, mitochondrial quality control
MeSH terms
PTEN-Induced Putative Kinase, Animals, Biological Transport, Disease Models, Animal, Drosophila melanogaster, Humans, Mitochondria, Models, Biological, Mutation, Neoplasms, Parkinson Disease, Protein Kinases, Apoptosis, Protein Folding, Oxidative Stress, Calcium Signaling, Mice, Ubiquitination

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