biostudies-literatureUnknown5(7)Gil-Pitarch CDrug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from patients with APAP-induced liver injury (AILI) and in mice treated with an APAP overdose. MLN4924, an inhibitor of the neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8)-activating enzyme (NAE-1), ameliorated necrosis and boosted liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 (^bioNEDD8) andCell reports. Medicine101653https://www.ebi.ac.uk/biostudies/studies/S-EPMC11293357biostudies-literatureNeddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway.PMC11293357Rodriguez-Agudo RMartinez-Cruz LAMercado-Gomez MReeves HLSimon JSutherland JDPena-Sanfelix PLachiondo-Ortega SPorcelli MAspichueta PMartinez-Chantar MLMosca LRejano-Gordillo CMMasson SIruzubieta PDelgado TCZapata-Pavas LEAzkargorta MLucena MIConter CNogueiras RSerrano-Macia MAndrade RJGonzalez-Recio ICrespo JGil-Pitarch CXirodimas DAurrekoetxea IGoikoetxea-Usandizaga NMcCain MVBarrio RMayor UElortza FfalseNeddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway.Drug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from patients with APAP-induced liver injury (AILI) and in mice treated with an APAP overdose. MLN4924, an inhibitor of the neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8)-activating enzyme (NAE-1), ameliorated necrosis and boosted liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 (^bioNEDD8) and2024-01-01T00:00:00Z2024 Jul2026-06-03T00:56:41.252Z2025-04-19T20:46:48.41ZS-EPMC112933573901900910.1016/j.xcrm.2024.101653