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Molecular Mechanisms of PINK1-Related Neurodegeneration

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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.

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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.

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Authors and Affiliations

  1. MRC Centre for Developmental and Biomedical Genetics, and Department of Biomedical Sciences, University of Sheffield, Sheffield, S10 2TN, UK

    Joe H. Pogson, Rachael M. Ivatt & Alexander J. Whitworth

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  1. Joe H. Pogson
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  2. Rachael M. Ivatt
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  3. Alexander J. Whitworth
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Correspondence to Alexander J. Whitworth.

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The first two authors contributed equally.

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Pogson, J.H., Ivatt, R.M. & Whitworth, A.J. Molecular Mechanisms of PINK1-Related Neurodegeneration. Curr Neurol Neurosci Rep 11, 283–290 (2011). https://doi.org/10.1007/s11910-011-0187-x

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