OMA1, DELE1 and HRI relay mitochondrial stress to the mammalian integrated stress response

The goal of this study is to understand how mamalian cells respond to the mitochondial stress. Using Quant-seq, we identifed an integrated stress response signature in the cells with compromized mitochondria. Furthermore, using an unbiased CRISPRi genetic screen, we uncovered a novel signaling pathway, in which OMA1, DELE1 and HRI are three major players that relay the mitochondrial stress to the integated stress response. To further study the cellular response in the absence of this pathway, we again used Quant-seq to uncover alternative pathways that might play a role during the mitochondrial stress response. The Quant-seq experiments were performed using HEK293T cells with OMA1, DELE1, HRI KD via CRISPRi under both untreated or 1.25 ng/mL oligomycin (16hrs) treated conditions with 3 replicates for each sample. For WT type cells, 50 ug/mL Doxycyline treated and untreated cells were also included for Quant-seq experiments with 2 replicates.