Abstract

Introduction: Mitochondrial function is key in cell bioenergetic and homeostasis by regulating ATP production and cell fate. During aging, the mitochondrial function is especially affected, contributing to hippocampal-dependent memory deterioration. Several reports showed that improving the mitochondrial function with mitochondrial metabolites enhances the memory processes. Moreover, the PKA pathway is critical for learning and spatial memory as well as for mitochondrial function. KDEL receptor (KDELR) is a Golgi-located receptor which activates PKA signaling and triggers a response in several organelles. In particular, the KDELR/PKA pathway coordinates the secretory and autophagy machinery to modulate lipid droplet turnover, suggesting that mitochondrial energy metabolism could be increased. Methodology: Mouse hippocampal HT22 cell line was used to perform live cell imaging and biochemical analyses to study the mitochondrial function after activation of the KDELR. Results: KDELR activation promotes mitochondrial subcellular relocation accompanied by an increase in the mitochondrial membrane potential, ATP production and mitochondrial ROS reduction. This KDELR-mediated enhancement in the mitochondrial function is dependent on PKA activity. Interestingly, KDELR is expressed mainly in the hippocampus of mice and its protein expression decreases with age. Discussion: We show that the KDELR is expressed in the hippocampus and its activation promotes the mitochondrial function, suggesting a possible role in memory processes. Thus, KDELR activation could be used to promote the mitochondrial function in the hippocampal neurons and attenuate the spatial memory loss in aging.