Cells respond dynamically and appropriately to various stress situations using a set of interconnected quality control pathways. For example, malfunctioning mitochondria are removed during stress conditions or nutrient limitation by mitophagy. The basis of this regulatory network governing the required adaptations as well as their hierarchy is largely unknown. The deubiquitinase complex Ubp3/Bre5 from S. cerevisiae is a key node linking a number of these quality control pathways. Here, we will apply in vivo and in vitro studies combined with synthetic switches and biosensors to decipher the molecular roles of Ubp3/Bre5 during intracellular stresses and altered mitochondrial energy metabolism.