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Current Neurology and Neuroscience Reports

, Volume 11, Issue 3, pp 283–290 | Cite as

Molecular Mechanisms of PINK1-Related Neurodegeneration

  • Joe H. Pogson
  • Rachael M. Ivatt
  • Alexander J. WhitworthEmail author
Article

Abstract

PINK1 is a mitochondrially targeted kinase that has been linked to a rare monogenic form of Parkinson’s disease (PD), a common neurodegenerative disease characterized by the degeneration of selected dopaminergic neurons. Intensive research using many model systems has clearly established a fundamental role for PINK1 in preventing mitochondrial dysfunction—a key mechanism long thought to play a central role in PD pathogenesis. Current hypotheses propose PINK1’s important functions involve mitophagy, mitochondrial calcium buffering, and mitochondrial quality control. Furthermore, recent findings have revealed that PINK1’s functions are likely regulated by a complex mechanism that includes regulated mitochondrial import and intramembrane proteolysis to influence its sub cellular and sub mitochondrial distribution. This review aims to summarize and evaluate recent findings, with particular emphasis on PINK1 localization, cleavage, and function in mitochondrial homeostasis.

Keywords

PINK1 Neurodegeneration Parkinson’s disease Kinase Parkin Mitochondrial dynamics Ubiquitination Mitophagy Autophagy Apoptosis Calcium buffering Mitofusin mtDNA Quality control Mitochondrial membrane potential Intramembrane proteolysis Rhomboid-7/PARL Mitochondrial trafficking Mitochondrial degradation CCCP Neuroprotection Milton Miro 

Notes

Acknowledgements

We apologize to colleagues whose work we were unable to cite due to space constraints. Work in the authors’ laboratory is supported in part by grants from the Wellcome Trust, European Framework 7, Parkinson’s UK, and the Wellcome/MRC Parkinson Disease Consortium grant to UCL/IoN, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee.

Disclosure

No potential conflicts of interest relevant to this article were reported.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Joe H. Pogson
    • 1
  • Rachael M. Ivatt
    • 1
  • Alexander J. Whitworth
    • 1
    Email author
  1. 1.MRC Centre for Developmental and Biomedical Genetics, and Department of Biomedical SciencesUniversity of SheffieldSheffieldUK

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