ERK-Mediated Phosphorylation of OLA1 Controls Adaptive Mitochondria to Nucleus Communication Regulating Cellular Homeostasis [CHIP-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. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) to define OLA1 interactions with DNA and identify putative OLA1 denovo binding motifs in the nucleus