Abstract

Introduction: Aging is the main risk factor for the development of neurodegenerative diseases. During aging a progressive deterioration of physiological functions occurs affecting the cerebral hippocampus and therefore, learning and spatial memory functions. One of the main factors that contributes to brain deterioration age-associated is the decrease of mitochondrial function, generating a deficiency in energy production, particularly important in the hippocampus (Jara et al., 2019). The functional deficit in the mitochondrial function can be prevented by dietary supplementation with mitochondrial metabolites, favoring ATP synthesis and controlled ROS production. The mitochondrial function is regulated by PKA/Src signaling, which increases β-oxidation and ATP production; which it is critical for learning and spatial memory. Under this context, KDELR is a new Golgi-located GPCR which activate a Gs-dependent PKA signaling (Pulvirenti et al., 2000 Giannotta et al., 2012 and Cancino et al., 2014) (Figure 1). ThisGolgi-originated signaling triggers a response in several organelles by a CREB-dependent transcriptional response (Cancino et al., 2014). In particular, the Gs / PKA pathway triggers a coordinated response between ER, Golgi, Lysosomes and autophagy to modulate lipid droplet turnover. We named this process TIDeRS, for Traffic-induced Degradation Response for Secretion (Tapia et al., 2019) (figure 1). The KDELR-dependent regulation of TIDeRS strongly suggest that mitochondrial energy metabolism could be regulated by signaling pathways starting from the Golgi complex. Hence, we have proposed the KDELR as a new mitochondrial regulator, suggesting a role during aging. Mouse hippocampal HT22 and HeLa cell line were used to performed live cell imaging using fluorescent probes together with biochemical analyses to study the mitochondrial function after activation of the KDELR. Material and Methods: Mouse hippocampal HT22 and HeLa cell line were used to performed live cell imaging using fluorescent probes together with biochemical analyses to study the mitochondrial function after activation of the KDELR. Results: By using multispectral confocal live cell imaging, we have found that the KDELR activation promotes the mitochondrial movement and relocation towards the perinuclear area in hippocampal-derived HT22 cell line. Along with these changes, we found increased mitochondrial membrane potential and ATP production. By western blot we have found tha the KDELR levels are decreased during aging in mice.