Lipotoxic effects in mitochondria are also mediated by JNK; high concentrations of palmitate cause mitochondrial dysfunction and apoptosis through phosphorylation of Sab (SH3BP5), a mitochondrial outer membrane substrate of JNK [124], whereas free cholesterol accumulation in the liver of NASH mice induces mitochondrial permeability, ROS production and apoptosis through JNK1. Here, SH3BP5 is linked to metabolic dysfunction-associated steatohepatitis.