Parkin is recruited to depolarized mitochondria for quarantine and removal of damaged mitochondria. Dysfunction of this process predisposes development of familial recessive Parkinson's disease. While various candidate molecules for the Parkin receptor have been proposed, all inadequately explain the accumulated data, thus the molecular basis for Parkin recruitment remains unknown. In this study, we show that a lysosomal phosphorylated polyubiquitin-chain recruited phosphomimetic Parkin to the lysosome. Furthermore, physical interactions between phosphomimetic Parkin and phosphorylated polyubiquitin-chain were detected both in vitro and in cells. We thus propose that the phosphorylated ubiquitin chain functions as the genuine Parkin receptor for recruitment to depolarized mitochondria.
Research Area “Elucidation and regulation in the dynamic maintenance and transfiguration of homeostasis in living body”
Research Theme “Elucidate the Parkinson's disease pathogenesis from a viewpoint of mitochondrial homeostatic control”
Kei Okatsu, Fumika Koyano, Mayumi Kimura, Hidetaka Kosako, Yasushi Saeki, Keiji Tanaka, and Noriyuki Matsuda. “Phosphorylated ubiquitin chain is the genuine Parkin receptor”. Journal of Cell Biology, Published on April 6, 2015, doi: 10.1083/jcb.201410050.
Noriyuki Matsuda, Ph.D.
Associate Director Researcher, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science
(Aforementioned URL is written in Japanese)
Koji Matsuo, Tetsu Kawaguchi, and Hideaki Inada
Life Innovation Group, Department of Innovation Research, JST