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Cited by 237Parkinson's Disease Mechanisms and TreatmentsAutophagy in Disease and TherapyNuclear Receptors and Signaling

PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson’s Disease Pathobiology?

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Truban, Dominika, Hou, Xu, Caulfield, Thomas R., Fiesel, Fabienne C., Springer, Wolfdieter·2016·Journal of Parkinson’s Disease
DOI 10.3233/jpd-160989PMC PMC5302033
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Abstract

The first clinical description of Parkinson’s disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy. It has become evident that there are many other aspects of this complex regulated, multifaceted pathway that provides neuroprotection. As such, numerous additional factors that impact PINK1/Parkin have already been identified including genes involved in other forms of PD. A great pathogenic overlap amongst different forms of familial, environmental and even sporadic disease is emerging that potentially converges at the level of mitochondrial quality control. Tremendous efforts now seek to further detail the roles and exploit PINK1 and Parkin, their upstream regulators and downstream signaling pathways for future translation. This review summarizes the latest findings on PINK1/Parkin-directed mitochondrial quality control, its integration and cross-talk with other disease factors and pathways as well as the implications for idiopathic PD. In addition, we highlight novel avenues for the development of biomarkers and disease-modifying therapies that are based on a detailed understanding of the PINK1/Parkin pathway.

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  • PINK1 accumulates on the OMM following MMP reduction, while it undergoes cleavage in healthy mitochondria due to proteasomal degradation.

    “PINK1, which accumulates on the OMM following MMP reduction, while it undergoes cleavage in healthy mitochondria due to proteasomal degradation5,8.”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [8]

    In “The Life Cycle of PINK1 – A Sensor for Mitochondrial Damage,” the paper says mitochondrial depolarization prevents import and full-length PINK1 accumulates on the OMM. It also says PINK1 is cleaved in healthy mitochondria, but cleavage is performed by mitochondrial proteases MPP and PARL; proteasomal degradation occurs afterward, rather than causing the cleavage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Ubiquitination/proteasomal degradation of Mfn1 and Tom40, as well as of total mitochondrial ubiquitin, are reduced in APOE4 astrocytes.

    “the ubiquitination/proteasomal degradation of Mfn1 and Tom408,35, as well as of total mitochondrial ubiquitin, are reduced in the APOE4 astrocytes”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [8]

    The PINK1/Parkin-Directed Mitochondrial Quality Control section says Mitofusin-1 is targeted for elimination via the 26 S proteasome. The passages found do not establish proteasomal degradation of Tom40 or reduced ubiquitination and degradation in APOE4 astrocytes. No page number was available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Cytosolic PRKN translocates to mitochondria and contributes to formation of mitochondrial pS65-Ub chains.

    “Cytosolic PRKN translocates to mitochondria and contributes to the formation of mitochondrial pS65-Ub chains [11].”

    From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [11]

  • Several pathways mediate mitophagy, including the PINK1/parkin pathway.

    “Several pathways mediate mitophagy, including the PINK1/parkin pathway5,8.”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [8]

  • During mitophagy, Mfn1 undergoes ubiquitination by parkin followed by proteasomal degradation, which suppresses mitochondrial fusion and allows removal of mitochondria from the network.

    “During mitophagy, Mfn1 undergoes ubiquitination by parkin followed by proteasomal degradation, which suppresses mitochondrial fusion and allows the removal of mitochondria from the network8.”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [8]

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Authors
Truban, D., Hou, X., Caulfield, T. R., Fiesel, F. C., & Springer, W.
Affiliations
  • Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
  • Mayo Clinic in Florida (US)
  • Mayo Clinic (US)
Corresponding author
Springer, Wolfdieter
ORCID
Venue
Journal of Parkinson’s Disease
Publisher
SAGE Publications
Published
2016-10-12
Volume
7
Issue
1
Pages
13-29
ISSN
  • 1877-7171 (ISSN-L)
  • 1877-718X
DOI
10.3233/jpd-160989
PMC
PMC5302033
OpenAlex
W2557944616
Cited by
237
References
195
Citations by year
2026: 13 · 2025: 17 · 2024: 25 · 2023: 21 · 2022: 19 · 2021: 40 · 2020: 40 · 2019: 26 · 2018: 22 · 2017: 14
FWCI
2.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Parkinson s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Parkinson Disease Association
  • National Institute of Neurological Disorders and Stroke (R01NS085070)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, PINK1, Parkin, mitochondrial quality control, mitophagy, mitochondrial dysfunction, familial Parkinson's disease, E3 ubiquitin ligase, neuroprotection, biomarkers, disease-modifying therapy, sporadic Parkinson's disease
MeSH terms
PTEN-Induced Putative Kinase, Animals, Humans, Mitochondria, Parkinson Disease, Protein Kinases, Ubiquitin-Protein Ligases

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 ›

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