Ubiquitin-dependent control of mitochondrial function: the reductive stress response

Michael Rape, University of California, Berkeley
Mitochondria are essential organelles that provide ATP and many metabolic building blocks, but also regulate crucial immune and cell survival pathways. Safeguarding mitochondrial function is therefore essential for development, and dysregulation of these organelles causes severe metabolic or neurodegenerative diseases. We recently discovered the reductive stress response, which detects mitochondrial inactivation by sensing the depletion of reactive oxygen species (ROS) that are usually produced by the electron transport chain. A persistent absence of ROS upon mitochondrial inactivation reduces the FNIP1 protein to allow for its redox-sensitive ubiquitylation and proteasomal degradation, which in turn activates mitochondria and allows them to produce both metabolites as well as ROS. I will discuss our discovery of the reductive stress response and present the structural basis and regulation of this conserved stress pathway that ensures mitochondrial integrity for robust development.