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Cited by 367Parkinson's Disease Mechanisms and TreatmentsAutophagy in Disease and TherapyMitochondrial Function and Pathology

Targeting Mitochondrial Dysfunction: Role for PINK1 and Parkin in Mitochondrial Quality Control

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Narendra, Derek P., Youle, Richard J.·2011·Antioxidants & Redox Signaling
DOI 10.1089/ars.2010.3799PMC PMC3078490
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Abstract

Mitochondria, which convert energy for the cell, accumulate damage with age, and the resulting mitochondrial dysfunction has been linked to the development of degenerative diseases and aging. To curb the accumulation of damaged mitochondria, the cell has elaborated a number of mitochondrial quality control processes. We describe recent work suggesting that Parkin and PTEN-induced putative kinase 1 (PINK1), two gene products linked to familial forms of parkinsonism, may constitute one of the cell's mitochondrial quality control pathways-identifying impaired mitochondria and selectively trimming them from the mitochondrial network by mitophagy. In particular, we discuss the regulation of PINK1 protein expression and Parkin localization by the bioenergetic status of individual mitochondria; the mechanism by which PINK1 recruits Parkin to the outer mitochondrial membrane; and Parkin's promotion of mitophagy through its ubiquitination of outer mitochondrial membrane proteins. This recent work suggests that Parkin and PINK1 may be among the first mammalian proteins identified with a direct role in regulating mitophagy, and implicate a failure of mitophagy in the pathogenesis of Parkinson's disease.

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References 57 · Cited by 367

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Authors
Narendra, D. P., & Youle, R. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Youle, Richard J.
ORCID
Venue
Antioxidants & Redox Signaling
Publisher
SAGE Publications
Published
2011-05-15
Volume
14
Issue
10
Pages
1929-1938
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
DOI
10.1089/ars.2010.3799
PMC
PMC3078490
OpenAlex
W2006578754
Cited by
367
References
57
Citations by year
2026: 12 · 2025: 13 · 2024: 17 · 2023: 32 · 2022: 16 · 2021: 24 · 2020: 29 · 2019: 21 · 2018: 24 · 2017: 15 · 2016: 24 · 2015: 22 · 2014: 33 · 2013: 32 · 2012: 38
FWCI
4.64
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
PINK1, Parkin, mitochondrial quality control, mitophagy, mitochondrial dysfunction, Parkinson's disease, ubiquitination, mitochondrial outer membrane, aging, degenerative diseases
MeSH terms
PTEN-Induced Putative Kinase, Animals, Autophagy, Humans, Mitochondria, Protein Kinases, Mitochondrial Proteins, Ubiquitin-Protein Ligases, Membrane Potential, Mitochondrial, Ubiquitination

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