Rebekka Lambrecht, Franziska Rudolf, Anna-Katharina Ückert, Valentina C Sladky, Truong San Phan, Jasmin Jansen, Samara Naim, Thomas Kaufmann, Adrian Keogh, Susanne Kirschnek, Aswin Mangerich, Florian Stengel, Marcel Leist, Andreas Villunger, Thomas Brunner
Paracetamol (acetaminophen, APAP) overdose severely damages mitochondria and triggers several apoptotic processes in hepatocytes, but the final outcome is fulminant necrotic cell death, resulting in acute liver failure and mortality. Here, we studied this switch of cell death modes and demonstrate a non-canonical role of the apoptosis-regulating BCL-2 homolog BIM/Bcl2l11 in promoting necrosis by regulating cellular bioenergetics. BIM deficiency enhanced total ATP production and shifted the bioenergetic profile towards glycolysis, resulting in persistent protection from APAP-induced liver injury...
November 24, 2023: Cell Death and Differentiation