ERK-Mediated Phosphorylation of OLA1 Controls Adaptive Mitochondria to Nucleus Communication Regulating Cellular Homeostasis [RNA-seq]

We found that changes in mitochondrial membrane potential or ROS generation trigger the translocation of OLA1 from mitochondria and cytoplasm to the nucleus, regulated by ERK1-mediated phosphorylation of OLA1 on Ser232/Tyr236. Subsequent phosphorylation of nuclear-OLA1 on Thre325 by ERK2 activates its function as a genetic factor regulating cellular homeostasis by modulating HDAC9 expression. Disruption of OLA1 phosphorylation blocks its nuclear translocation, compromised the expression of nuclear-encoded mitochondrial proteins, DNA damage response, and multiple stress-response-related-genes, leading to cellular dysfunction. Our findings reveal that OLA1 is a crucial component of mitonuclear response regulatory hubs essential for regulating cellular adaptation to stress. Examination of the effect of OLA1 knockdown and OLA1 nuclear localization on gene expression in pulmonary endothelial cells.