Phoenixin 20 promotes neuronal mitochondrial biogenesis via CREB –PGC-1α pathway

This study showed that the presence of Phoenixin 20 promoted neuronal mitochondrial biogenesis in vitro. In cultured neuronal M17 cells, Phoenixin 20 increased the expression of mitochondrial regulators PGC-1 α, NRF-1, and TFAM at both mRNA and protein levels. The treatment of Phoenixin 20 increased the ratio of mitochondrial vs nuclear DNA (mtDNA/nDNA) and the multiple mitochondrial gene expression as revealed by increasing mRNA expression of Tomm22, Timm50, Atp5d, Ndufs3, and protein expression of NDU FB8. At a cellular level, Phoenixin 20 promoted mitochondrial respiratory rate and cellular ATP production. Mechanistically, we found that Phoenixin 20 induced the phosphorylation of CREB, which suggests that Phoenixin 20 promoted the activation of the CREB pathway. The blockage of CREB by its selec tive inhibitor H89 prevented the effect of Phoenixin 20 on mitochondrial regulators and biogenesis. Moreover, the study showed that Phoenixin 20 induced the expression of its tentative receptor GPR173 at the mRNA and protein level, and the silence of GPR173 in neuronal cells ablated all its effect o n mitochondrial regulation. Collectively, we showed that Phoenixin 20 promoted neuronal mitochondrial biogenesis via the regulation of CREB–PGC-1α pathway. This study revealed a new role and underlying mechanism of Phoenixin 20 in neuronal cells, suggesting it influences the therapeutic implicati on of neurodegenerative diseases.
Source: Journal of Molecular Histology - Category: Laboratory Medicine Source Type: research