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Course, M.M., Scott, A.I., Schoor, C., Hsieh, C.H., Papakyrikos, A.M., Winter, D., Cowan, T.M., Wang, X. (2018). Phosphorylation of MCAD selectively rescues PINK1 deficiencies in behavior and metabolism.  Mol. Biol. Cell 29(10): 1219--1227.
FlyBase ID
FBrf0238892
Publication Type
Research paper
Abstract

PTEN-induced putative kinase 1 (PINK1) is a mitochondria-targeted kinase whose mutations are a cause of Parkinson's disease. We set out to better understand PINK1's effects on mitochondrial proteins in vivo. Using an unbiased phosphoproteomic screen in Drosophila, we found that PINK1 mediates the phosphorylation of MCAD, a mitochondrial matrix protein critical to fatty acid metabolism. By mimicking phosphorylation of this protein in a PINK1 null background, we restored PINK1 null's climbing, flight, thorax, and wing deficiencies. Owing to MCAD's role in fatty acid metabolism, we examined the metabolic profile of PINK1 null flies, where we uncovered significant disruptions in both acylcarnitines and amino acids. Some of these disruptions were rescued by phosphorylation of MCAD, consistent with MCAD's rescue of PINK1 null's organismal phenotypes. Our work validates and extends the current knowledge of PINK1, identifies a novel function of MCAD, and illuminates the need for and effectiveness of metabolic profiling in models of neurodegenerative disease.

PubMed ID
PubMed Central ID
PMC5935071 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Biol. Cell
    Title
    Molecular Biology of the Cell
    Publication Year
    1992-
    ISBN/ISSN
    1059-1524
    Data From Reference
    Aberrations (1)
    Alleles (11)
    Genes (3)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (2)
    Transgenic Constructs (7)