Arrestin‐3 binds parkin and enhances parkin‐dependent mitophagy

• DOI: 10.1111/jnc.16043
• Publication Date: 2024-01-10T07:24:47Z
• Authors: Chen Zheng; Kevin K. Nguyen; Sergey A. Vishniv...; Vsevolod V. Gurevich; Eugenia V. Gurevich
• Keywords: Arrestin

Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins shown to regulate several signaling pathways. Some these pathways require arrestin binding GPCRs, the regulation others is receptor independent. Here, we demonstrate that arrestin-3 binds E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification domains involved suggests likely relieves autoinhibition and/or stabilizes enzymatically active "open" conformation parkin. Arrestin-3 enhances ubiquitination by mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy HeLa cells. Furthermore, mutant enhanced rescue presence Parkinson's disease-associated R275W mutant, which defective both functions. Thus, modulation activity might be a novel strategy anti-parkinsonian therapy.