Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin

Nicole Exner, Bettina Treske, Dominik Paquet, Kira Holmström, Carola Schiesling, Suzana Gispert, Iria Carballo-Carbajal, Daniela Berg, Hans Hermann Hoepken, Thomas Gasser, Rejko Krüger, Konstanze F. Winklhofer, Frank Vogel, Andreas S. Reichert, Georg Auburger, Philipp J. Kahle, Bettina Schmid, Christian Haass*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

447 Citations (Scopus)


Degeneration of dopaminergic neurons in the substantia nigra is characteristic for Parkinson's disease (PD), the second most common neurodegenerative disorder. Mitochondrial dysfunction is believed to contribute to the etiology of PD. Although most cases are sporadic, recent evidence points to anumber of genes involved in familial variants of PD. Among them, a loss-of-function of phosphatase and tensin homolog-induced kinase 1 (PINK1; PARK6) is associated with rare cases of autosomal recessive parkinsonism. In HeLa cells, RNA interference-mediated downregulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Morphological changes of mitochondria can be rescued by expression of wild-type PINK1 but not by PD-associated PINK1 mutants. Moreover, primary cells derived from patients with two different PINK1 mutants showed a similar defect in mitochondrial morphology. Human parkin but not PD-associated mutants could rescue mitochondrial pathology in human cells like wild-type PINK1. Our results may therefore suggest that PINK1 deficiency in humans results in mitochondrial abnormalities associated with cellular stress, a pathological phenotype, which can be ameliorated by enhanced expression of parkin.

Original languageEnglish
Pages (from-to)12413-12418
Number of pages6
JournalJournal of Neuroscience
Issue number45
Publication statusPublished - 7 Nov 2007
Externally publishedYes


  • Familial Parkinson's disease
  • Loss-of-function
  • Mitochondria
  • Neurodegeneration
  • PINK1
  • Parkin


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