With the development of the mePROD method, we were able to monitor translation changes globally under stress conditions. We used this method extensively to characterize different cellular stress responses. Key outcomes of our work was to reveal that the integrated stress response and mTOR cause inhibition of a largely overlapping set of proteins and that the mRNA of proteins, whose translation is controlled by the integrated stress response and mTOR, contains some intrinsic factors that drive their sensitivity to these pathways. Importantly, these results revealed how cellular stress reshapes the mitochondrial proteome and proteostasis. We are further examining these results and expect to identify how UPRmt activation leads to changes in the mitochondrial proteome via these pathways. To understand the direct effects on mitochondria, we expect to define the architecture, based on protein-protein interactions, of the RNA-processing structures within mitochondria. We already gained extensive insight in these and are expecting to also reveal changes in these structures during stress and to define their contribution to proteostasis. In addition, we plan to further define the outcome of UPRmt on neighboring cells. We expect to gain insight into the signaling molecular involved and to define the pathways activated or inhibited in recipient cells. Ultimately, we project to establish relevant model cells with disease-relevant mutations that serve as basis to examine the identified effects of the UPRmt within these cells.