Mass Spectrometry Analysis of c- Jun N -Terminal Kinase -Mediated Mitochondrial Protein Phosphorylation in Liver Injury

摘要

JNK -mediated cell damage has been observed with many toxic compounds such as acetaminophen (APAP) and carbon tetrachloride (CCl_4). Recently, we reported that CCl_4 rapidly activated JNK (p -JNK), which was translocated to mito chondria and inactivated mitochondrial aldehyde dehydrogenase (ALDH2) by phosphorylation. Thus, we hypothesized that p-JNK, activated at early hours after CCl_4 exposure, phosphorylates many mitochondrial proteins and suppresses their functions, contributin g to mitochondrial dysfunction and necrotic liver damage. In this study, we investigate d the mechanism of liver injury by identifying and characterizing mitochondrial JNK-target proteins and studying the ir roles in mouse models of acute liver injury induced by the hepatotoxic agent s CCl_4 and APAP.