Impaired Mitophagy and Protein Acetylation Levels in Fibroblasts from Parkinson's Disease Patients.

Molecular Neurobiology
Sokhna M S Yakhine-DiopJosé M Fuentes

Abstract

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. While most PD cases are idiopathic, the known genetic causes of PD are useful to understand common disease mechanisms. Recent data suggests that autophagy is regulated by protein acetylation mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities. The changes in histone acetylation reported to be involved in PD pathogenesis have prompted this investigation of protein acetylation and HAT and HDAC activities in both idiopathic PD and G2019S leucine-rich repeat kinase 2 (LRRK2) cell cultures. Fibroblasts from PD patients (with or without the G2019S LRRK2 mutation) and control subjects were used to assess the different phenotypes between idiopathic and genetic PD. G2019S LRRK2 mutation displays increased mitophagy due to the activation of class III HDACs whereas idiopathic PD exhibits downregulation of clearance of defective mitochondria. This reduction of mitophagy is accompanied by more reactive oxygen species (ROS). In parallel, the acetylation protein levels of idiopathic and genetic individuals are different due to an upregulation in class I and II HDACs. Despite this upregulation, the total HDAC activity is decrease...Continue Reading

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Citations

Jun 19, 2020·Antioxidants·Eva Alegre-CortésSokhna M S Yakhine-Diop
Feb 15, 2019·Neural Regeneration Research·Sokhna M S Yakhine-DiopJosé M Fuentes
Oct 3, 2020·International Journal of Molecular Sciences·Rui WangHaigang Ren
Dec 30, 2020·The Journal of Biological Chemistry·Emily H ClarkThomas Briston
Dec 8, 2019·European Journal of Medicinal Chemistry·Nadia A KhalilEman A Sobh
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Oct 15, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xinnan LiYing Peng
Nov 24, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Cláudia M DeusPaulo J Oliveira
Jan 8, 2021·The Journal of Biological Chemistry·Emily H ClarkThomas Briston
May 1, 2021·International Journal of Molecular Sciences·Laura DobladoMaria Monsalve
May 1, 2021·Cells·Liesel GoveasJean-Marc Taymans
Jun 2, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yuexia LiuChao Sun
Jun 3, 2021·Antioxidants·Anna De GaetanoMarcello Pinti

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Methods Mentioned

BETA
acetylation
histone acetylation
FACS
confocal microscopy
transfection
lipidation
flow cytometry
PCA

Software Mentioned

ImageJ
Ifdotmeter®

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