Global S&T Development Trend Analysis Platform of Resources and Environment
In mammalian cells, mitochondrial dysfunction triggers the integrated stress response, in which the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) results in the induction of the transcription factor ATF4(1-3). However, how mitochondrial stress is relayed to ATF4 is unknown. Here we show that HRI is the eIF2 alpha kinase that is necessary and sufficient for this relay. In a genome-wide CRISPR interference screen, we identified factors upstream of HRI: OMA1, a mitochondrial stress-activated protease
A genome-wide CRISPR interference screen shows that a signalling pathway involving OMA1, DELE1 and the eIF2 alpha kinase HRI relays mitochondrial stress to the cytosol to trigger the integrated stress response.
