UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
PINK1 cleavage at position A103 by the mitochondrial protease PARL.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SHY, Renton AEM, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW
  • Publication date:
    01/03/2011
  • Pagination:
    867, 879
  • Journal:
    Hum Mol Genet
  • Volume:
    20
  • Issue:
    5
  • Status:
    Published
  • Country:
    England
  • PII:
    ddq526
  • Language:
    eng
  • Keywords:
    Amino Acid Sequence, Cell Line, Humans, Metalloproteases, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Parkinson Disease, Parkinsonian Disorders, Protein Binding, Protein Kinases, Protein Processing, Post-Translational, Sequence Alignment
Abstract
Mutations in PTEN-induced kinase 1 (PINK1) cause early onset autosomal recessive Parkinson's disease (PD). PINK1 is a 63 kDa protein kinase, which exerts a neuroprotective function and is known to localize to mitochondria. Upon entry into the organelle, PINK1 is cleaved to produce a ∼53 kDa protein (ΔN-PINK1). In this paper, we show that PINK1 is cleaved between amino acids Ala-103 and Phe-104 to generate ΔN-PINK1. We demonstrate that a reduced ability to cleave PINK1, and the consequent accumulation of full-length protein, results in mitochondrial abnormalities reminiscent of those observed in PINK1 knockout cells, including disruption of the mitochondrial network and a reduction in mitochondrial mass. Notably, we assessed three N-terminal PD-associated PINK1 mutations located close to the cleavage site and, while these do not prevent PINK1 cleavage, they alter the ratio of full-length to ΔN-PINK1 protein in cells, resulting in an altered mitochondrial phenotype. Finally, we show that PINK1 interacts with the mitochondrial protease presenilin-associated rhomboid-like protein (PARL) and that loss of PARL results in aberrant PINK1 cleavage in mammalian cells. These combined results suggest that PINK1 cleavage is important for basal mitochondrial health and that PARL cleaves PINK1 to produce the ΔN-PINK1 fragment.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Clinical and Movement Neurosciences
Author
Clinical and Movement Neurosciences
Author
UCL School of Pharmacy
Author
Neurodegenerative Diseases
Author
Clinical and Movement Neurosciences
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by