Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons

• DOI: 10.1038/s42255-024-01007-w
• Publication Date: 2024-03-19T11:02:05Z
• Authors: J. Tabitha Hees; Simone Wanderoy; Jana Lindner; Marlena Helms; Hariharan Murali ...; Angelika B. Harbauer
• Keywords: PINK1

Abstract Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization PTEN-induced kinase 1 (PINK1) requires transport Pink1 messenger RNA (mRNA) tethering it to the mitochondrial surface. Here, we report that inhibition AMP-activated protein (AMPK) activation insulin signalling cascade prevents mRNA binding mitochondria. Mechanistically, AMPK phosphorylates anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site necessary for interaction with RNA-binding SYNJ2. Notably, loss association upon addition required PINK1 and function as ubiquitin mitophagy pathway, thus placing under metabolic control. Induction resistance vitro key genetic Alzheimer risk factor apolipoprotein E4 retains at proper activity, especially neurites. Our results identify switch controlling localization activity via neurons propose mechanistic connection between dysfunction.