Iris Wu L&S Sciences
Identifying a Mitokine Factor Involved in Cell-Non-Autonomous UPRmt Signaling
Several age-related neurodegenerative diseases are a result of a decline in protein homeostasis as organisms age. Mitochondria, a vital organelle in the cell, is especially susceptible and thought to be a sensor of proteotoxic stress. Understanding how mitochondria communicate stress and recover homeostasis is therefore fundamental in developing novel treatments for age-onset human diseases. One way that mitochondria communicate stress is through the mitochondrial unfolded protein response (UPRmt). Important work has shown that stress can be communicated between tissues, such as from neurons to intestinal cells, called the cell-non-autonomous UPRmt. However, how stress is communicated is not entirely known. It is postulated that an unknown factor termed mitokine is responsible for the stress signal communication. My project will identify a mitokine factor in cell-non-autonomous UPRmt using an EMS mutagenesis forward genetics screen in Caenorhabditis elegans. I hypothesize that an identified mitokine will be both necessary and sufficient to specifically induce UPRmt, and therefore, characterizing the identity of mitokine will reveal key insights into the mechanism of UPRmt, and in turn, how UPRmt confers organismal health.