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Cited by 184Parkinson's Disease Mechanisms and TreatmentsAutophagy in Disease and TherapyNuclear Receptors and Signaling

Regulation of PINK1-Parkin-mediated mitophagy

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Springer, Wolfdieter, Kahle, Philipp J.·2011·Autophagy
DOI 10.4161/auto.7.3.14348
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Abstract

Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.

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  • Upon mitochondrial damage, PINK1 is quickly stabilized on damaged mitochondria, leading to translocation of cytosolic Parkin to damaged mitochondria.

    “Upon mitochondrial damage, PINK1 is quickly stabilized on damaged mitochondria, which leads to translocation of cytosolic Parkin to damaged mitochondria [11–13].”

    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 [11]

    In “The PINK1-Parkin-Mediated Control of Mitochondrial Degradation” (page unavailable), the paper says full-length PINK1 is stabilized on depolarized mitochondria, resulting in Parkin recruitment, and describes Parkin as cytosolic. It does not support “quickly”: the same section says PINK1 levels gradually rise on depolarized mitochondria. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • PINK1 and Parkin functionally mediate stress-activated selective clearance of impaired mitochondria via autophagic degradation (mitophagy).

    “Together, they functionally mediate the stress-activated, selective clearance of impaired mitochondria via autophagic degradation (termed mitophagy) [11]”

    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 [11]

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Cited by

Sorted by citations

Authors
Springer, W., & Kahle, P. J.
Affiliations
  • Hertie Institute for Clinical Brain Research (DE)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
  • Springer, Wolfdieter
  • Kahle, Philipp J.
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2011-03
Volume
7
Issue
3
Pages
266-278
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.4161/auto.7.3.14348
OpenAlex
W1983509809
Cited by
184
References
0
Citations by year
2026: 12 · 2025: 8 · 2024: 13 · 2023: 14 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 9 · 2017: 8 · 2016: 21 · 2015: 5 · 2014: 17 · 2013: 12 · 2012: 9
FWCI
1.78
Type
journal article
Language
en
Open access
Locations
  • Autophagy (publishedVersion)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion)
Funders
  • Eberhard Karls Universität Tübingen
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
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
PINK1, Parkin, mitophagy, Parkinson's disease, mitochondrial quality control, neurodegeneration, therapeutic target
MeSH terms
PTEN-Induced Putative Kinase, Animals, Autophagy, Humans, Mitochondria, Parkinson Disease, Protein Kinases, Ubiquitin-Protein Ligases, Proteolysis

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