v-ATPase-mediated buffering of mitochondrial dysfunction
Mitochondrial dysfunction is implicated in a broad spectrum of human disease including primary mitochondrial disorders, neurodegeneration, cancer, and ageing. Cells have evolved several mechanisms in response to mitochondrial dysfunction to maintain cellular homeostasis and face fundamental challenges orchestrating the expression of the nuclear and mitochondrial genome. Here we used genome-wide CRISPR/Cas9 knockout screening in HEK293 to identify activated cell fitness pathways in response to distorted mitochondrial protein synthesis promoting cell survival upon mitochondrial dysfunction. Overall design: HEK293 cells were treated with low doses of actinonin, chlormaphenicol and the combination over 15-days using the Brunello GeCKO library. The samples encompass day 15 sequencing results of EtOH-treated control and the respective treatments in independent replicates.