New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases.

The c-Jun-N-terminal-kinase (JNK) family is highly conserved across species such as Drosophila, C. elegans, zebrafish and mammals, and plays a central role in hepatic physiologic and pathophysiologic responses. These responses range from cell death to cell proliferation and carcinogenesis, as well as metabolism and survival, depending on the specific context and duration of activation of the JNK signaling pathway.

c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)-dependent pathway leading to inactivation of intramitochondrial Src.

Unlabelled: Sustained c-Jun N-terminal kinase (JNK) activation has been implicated in many models of cell death and tissue injury. Phosphorylated JNK (p-JNK) interacts with the mitochondrial outer membrane SH3 homology associated BTK binding protein (Sab, or SH3BP5). Using knockdown or liver-specific deletion of Sab, we aimed to elucidate the consequences of this interaction on mitochondrial function in isolated mitochondria and liver injury models in vivo.