Stressed to death: Mitochondrial stress responses connect respiration and apoptosis in cancer

• Published in: Molecular cell Vol. 82; no. 18; pp. 3321 - 3332
• Main Authors: Winter, Jacob M., Yadav, Tarun, Rutter, Jared
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2022
• Subjects: Apoptosis; cancer; cancer therapy; CRISPR; death; electron transport chain; Humans; integrated stress response; leukemia; mitochondria; Mitochondria - metabolism; Neoplasms - genetics; Neoplasms - metabolism; oncology; oxidative phosphorylation; Oxidative Stress; Respiration; Signal Transduction; stress; stress response; venetoclax; stress; leukemia; CRISPR; electron transport chain; mitochondria; apoptosis; cancer; respiration; venetoclax; oxidative phosphorylation; oncology; integrated stress response
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2022.07.012

Mitochondrial energetics and respiration have emerged as important factors in how cancer cells respond to or evade apoptotic signals. The study of the functional connection between these two processes may provide insight into following questions old and new: how might we target respiration or downstream signaling pathways to amplify apoptotic stress in the context of cancer therapy? Why are respiration and apoptotic regulation housed in the same organelle? Here, we briefly review mitochondrial respiration and apoptosis and then focus on how the intersection of these two processes is regulated by cytoplasmic signaling pathways such as the integrated stress response. Aerobic respiration and apoptosis are two of the most characteristic activities performed by mitochondria. Here, we review how they are functionally interconnected via stress signaling pathways and describe how these connections might be exploited in the context of cancer therapy.