Mitochondrial stress is relayed to the cytosol by an OMA1–DELE1–HRI pathway

• Published in: Nature (London) Vol. 579; no. 7799; pp. 427 - 432
• Main Authors: Guo, Xiaoyan, Aviles, Giovanni, Liu, Yi, Tian, Ruilin, Unger, Bret A., Lin, Yu-Hsiu T., Wiita, Arun P., Xu, Ke, Correia, M. Almira, Kampmann, Martin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2020; Nature Publishing Group
• Subjects: 13; 13/106; 13/31; 14; 14/63; 38; 42; 45; 45/47; 631/80/642/333; 631/80/86/2366; 82; 82/1; 82/29; 82/51; 82/58; 82/83; Activating Transcription Factor 4 - biosynthesis; Activating Transcription Factor 4 - metabolism; Amino acids; Cell Line; Cell physiology; Cellular stress response; Chaperones; CRISPR; CRISPR-Cas Systems; Cytosol; Cytosol - enzymology; Cytosol - metabolism; eIF-2 Kinase - metabolism; Enzyme Activation; Eukaryotic Initiation Factor-2 - metabolism; Genetic aspects; Genomes; Health aspects; Humanities and Social Sciences; Humans; Initiation factor eIF-2; Kinases; Localization; Male; Mammalian cells; Metalloendopeptidases - metabolism; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - metabolism; Molecular Chaperones - metabolism; multidisciplinary; Phosphorylation; Physiological aspects; Physiological research; Protein Binding; Proteins; Science; Science (multidisciplinary); Stress (Physiology); Stress, Physiological; Therapeutic applications; United States

In mammalian cells, mitochondrial dysfunction triggers the integrated stress response, in which the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) results in the induction of the transcription factor ATF4 1 – 3 . However, how mitochondrial stress is relayed to ATF4 is unknown...