Fig. 6

ER-stress promotes mitochondrial TrkAIII translocation, activation and the Warburg effect. Schematic representation of: a) ER stress induced translocation of MAM-associated TrkAIII into mitochondrial inner membranes, resulting in Omi/HtrA2-dependent TrkAIII cleavage activation, PDHK1 tyrosine phosphorylation and aerobic glycolytic “Warburg” metabolic adaptation, involving ER Ca2+ release and uptake by mitochondria and increased ROS production, within the context of mitochondria protected against apoptosis by increased Bcl-2 proteins and SOD2 expression, and b) The effect of Trk tyrosine kinase inhibitor on ER stress-induced mitochondrial TrkAIII translocation and cleavage but inactivation, leading to reduced Warburg metabolic adaptation and increased apoptosis, associated with reduced Bcl-2 protein and SOD2 expression