Mitochondrial FNIP1 Recruitment in the Reductive Stress Response
Redox homeostasis is essential for cell health. It can be perturbed by an overproduction of reactive oxygen species (ROS), which leads to oxidative stress. The converse, reductive stress, is caused by mitochondrial inactivation and depletion of ROS. Persistent reductive stress impairs metazoan development and causes cancer, diabetes, and cardiomyopathy. Despite its central role in development and disease, how reductive stress is sensed and alleviated remains poorly understood. The Rape Lab recently identified the first pathway that can counteract reductive stress. Following reductive stress, the E3 ligase CUL2FEM1B marks the FNIP1 proteins for degradation at the outer mitochondrial membrane, which increases electron transport chain activity and resupplies cells with ROS. I hypothesize that localized FNIP1 degradation allows the reductive stress pathway to accurately sense mitochondrial ROS production. The primary goal of my SURF project is to determine how FNIP1 is recruited to the mitochondria. This is essential to understanding how a localized stress pathway operates to control mitochondrial activity and ensure robust development.
Message to Sponsor
- Major: Molecular and Cellular Biology
- Sponsor: Guthrie Fund
- Mentor: Michael Rape