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Parkinson Disease: HELP
Articles by Liesbeth Aerts
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Liesbeth Aerts wrote the following 3 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review PINK1 activation-turning on a promiscuous kinase. 2015

Aerts, Liesbeth / De Strooper, Bart / Morais, Vanessa A. ·*Center for Human Genetics, LIND and KU Leuven, O&N1 Herestraat 49 box 602, 3000 Leuven, Belgium. ·Biochem Soc Trans · Pubmed #25849930.

ABSTRACT: PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a serine/threonine kinase targeted to mitochondria and implicated in early-onset recessive Parkinson's disease (PD). Through the phosphorylation of its downstream targets, PINK1 regulates multiple mitochondrial processes, including ATP production, stress-response and mitochondrial dynamics and quality control. The orchestration of such a wide array of functions by an individual kinase requires a fine-tuned and versatile regulation of its activity. PINK1 proteolytic processing, trafficking and localization, as well as different post-translational modifications, affect its activity and function. Unravelling the regulatory mechanisms of PINK1 is essential for a full comprehension of its kinase function in health and disease.

2 Article PINK1 kinase catalytic activity is regulated by phosphorylation on serines 228 and 402. 2015

Aerts, Liesbeth / Craessaerts, Katleen / De Strooper, Bart / Morais, Vanessa A. ·From the Center for the Biology of Disease, Flemish Institute for Biotechnology (VIB) and Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders and University Hospitals Leuven, University of Leuven, 3000 Leuven, Belgium and. · From the Center for the Biology of Disease, Flemish Institute for Biotechnology (VIB) and Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders and University Hospitals Leuven, University of Leuven, 3000 Leuven, Belgium and the University College London, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom. · From the Center for the Biology of Disease, Flemish Institute for Biotechnology (VIB) and Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders and University Hospitals Leuven, University of Leuven, 3000 Leuven, Belgium and Vanessa.Morais@cme.vib-kuleuven.be. ·J Biol Chem · Pubmed #25527497.

ABSTRACT: Mutations in the PINK1 gene cause early-onset recessive Parkinson disease. PINK1 is a mitochondrially targeted kinase that regulates multiple aspects of mitochondrial biology, from oxidative phosphorylation to mitochondrial clearance. PINK1 itself is also phosphorylated, and this might be linked to the regulation of its multiple activities. Here we systematically analyze four previously identified phosphorylation sites in PINK1 for their role in autophosphorylation, substrate phosphorylation, and mitophagy. Our data indicate that two of these sites, Ser-228 and Ser-402, are autophosphorylated on truncated PINK1 but not on full-length PINK1, suggesting that the N terminus has an inhibitory effect on phosphorylation. We furthermore establish that phosphorylation of these PINK1 residues regulates the phosphorylation of the substrates Parkin and Ubiquitin. Especially Ser-402 phosphorylation appears to be important for PINK1 function because it is involved in Parkin recruitment and the induction of mitophagy. Finally, we identify Thr-313 as a residue that is critical for PINK1 catalytic activity, but, in contrast to previous reports, we find no evidence that this activity is regulated by phosphorylation. These data clarify the regulation of PINK1 through multisite phosphorylation.

3 Article PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. 2014

Morais, Vanessa A / Haddad, Dominik / Craessaerts, Katleen / De Bock, Pieter-Jan / Swerts, Jef / Vilain, Sven / Aerts, Liesbeth / Overbergh, Lut / Grünewald, Anne / Seibler, Philip / Klein, Christine / Gevaert, Kris / Verstreken, Patrik / De Strooper, Bart. ·VIB Center for the Biology of Disease, 3000 Leuven, Belgium. ·Science · Pubmed #24652937.

ABSTRACT: Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations.