The Mitochondrial Stress Response in Human Cells and its Relevance to Aging
Mitochondria are essential for eukaryotic cell. Mitochondria are not only the metabolic hub, but also involved in many signaling pathways. One prevalent theory of aging is that accumulation of damaged mitochondria contributes to aging and to neurodegenerative diseases. The objective of this project is to systematically elucidate how human cells respond to damaged mitochondria and to characterize this response during aging. In mammalian cells, mitochondrial dysfunction trigger the integrated stress response, in which phosphorylation of eIF2α up-regulates a transcriptional factor ATF4. However, the link between mitochondrial dysfunction and the integrated stress response is missing. Using an unbiased CRISPRi genetic screen, I will identify genetic factors that relay the mitochondrial dysfunction to the integrated stress response. Identification such pathways will provide potential therapeutic targets for aging and aging-associated diseases.