Deletion of ABIN1-LIR motifs impairs hepatic lipid homeostasis and mitophagy via AMPK-TFEB axis in mice
Year: 2025
Type: article
Abstract: Having identified LC3-interacting region (LIR) motifs 1/2 of A20 binding inhibitor of NF-κB-1 (ABIN-1) as mitophagy regulators in vitro, this study generated CRISPR-engineered ABIN1-ΔLIR1/2 mice lacking both LIR motifs to elucidate its in vivo significance. These mice exhibit enhanced hepatic lipid droplet accumulation, dysregulated mitochondrial metabolism, and impaired mitophagy, through modulation of the AMPK-TFEB axis. Liver biopsies from patients with metabolic dysfunction-associated steatotic liver disease corroborate these findings, suggesting therapeutic implications for liver diseases.
Authors: Lisa Sophie Huber, Rosetta Merline, Jinyang Zeng-Brouwers, Rajkumar Vutukuri, Nico Kraus, Cristina Ortiz, Stefan Guenther, Eva Miriam Buhl, Lisa Hahnefeld, Robert Gurke, Julia Bein, Madina Karimova, Patrick Wurzel, Peter Boor, Christoph Welsch, Peter Wild, Josef Pfeilschifter, Donat Kögel, Malgorzata Wygrecka, Jonel Trebicka, Rafal Bartoszewski, Ivan Dikic, Liliana Schaefer
Institutions: Goethe University Frankfurt, University Hospital Frankfurt, Max Planck Institute for Heart and Lung Research, Universitätsklinikum Aachen, RWTH Aachen University, Fraunhofer Institute for Translational Medicine and Pharmacology, Georg Speyer Haus, German Center for Lung Research, Universities of Giessen and Marburg Lung Center, European Foundation for the Study of Chronic Liver Failure, University Hospital Münster, University of Wrocław
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1462112011, G2013436488, Die Rolle von epithelialen CD74 in Nierenerkrankungen, G2821785707, G2906592815, G410390351, G5290293035, KFO 5011: Integration neuer Methoden zur Verbesserung von translationaler Nierenforschung, G551519423, TRR 219: Mechanismen kardiovaskulärer Komplikationen bei chronischer Niereninsuffizienz
OpenAlex ID: W4414080115