Phosphorylation of Optineurin by protein kinase D regulates Parkin-dependent mitophagy
Year: 2024
Type: article
Abstract: Degradation of damaged mitochondria, a process called mitophagy, plays a role in mitochondrial quality control and its dysfunction has been linked to neurodegenerative pathologies. The PINK1 kinase and the ubiquitin ligase Parkin-mediated mitophagy represents the most common pathway in which specific receptors, including Optineurin (Optn), target ubiquitin-labeled mitochondria to autophagosomes. Here, we show that Protein Kinases D (PKD) are activated and recruited to damaged mitochondria. Subsequently, PKD phosphorylate Optn to promote a complex with Parkin leading to enhancement of its ubiquitin ligase activity. Paradoxically, inhibiting PKD activity enhances the interaction between Optn and LC3, promotes the recruitment of Parkin to mitochondria, and increases the mitophagic function of Optn. This enhancement of mitophagy is characterized by increased production of mitochondrial ROS and a reduction in mitochondrial mass. The PKD kinases may therefore regulate Optn-dependent mitophagy by amplifying the Parkin-mediated degradation signals to improve the cell response against oxidative stress damage.
Source: iScience
Authors: Robert Weil, Emmanuel Laplantine, Messaouda Attailia, Anne Oudin, Shannel Curic, Aya Yokota, Elie Banide, Pierre Génin
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, Centre National de la Recherche Scientifique, Cancéropôle Ile de France, Sorbonne Université, National Institutes of Health, RIKEN, Centre International de Mathématiques et Informatique de Toulouse, Institut des sciences biologiques, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W4404338550