PINK1 and Parkin – mitochondrial interplay between phosphorylation and ubiquitylation in Parkinson's disease

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Abstract
The discovery of mutations in genes encoding protein kinase PTEN‐induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin in familial Parkinson's disease and their association with mitochondria provides compelling evidence that mitochondrial dysfunction is a major contributor to neurodegeneration in Parkinson's disease. In recent years, tremendous progress has been made in the understanding of how PINK1 and Parkin enzymes are regulated and how they influence downstream mitochondrial signalling processes. We provide a critical overview of the key advances in the field and also discuss the outstanding questions, including novel ways in which this knowledge could be exploited to develop therapies against Parkinson's disease.
Funding Information
  • J. Macdonald Menzies Charitable Trust Prize Studentship
  • Wellcome Trust Senior Research Fellowship in Clinical Science (101022/Z/13/Z)
  • Medical Research Council
  • The Wellcome Trust
  • Parkinson's UK
  • the Michael J. Fox Foundation for Parkinson's disease
  • Wellcome/MRC PD consortium
  • AstraZeneca
  • Boehringer-Ingelheim
  • GlaxoSmithKline
  • Merck KGaA
  • Janssen Pharmaceutica
  • Pfizer

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