Where does the UPR function? Between the endoplasmic reticulum (ER) and the nucleus of eukaryotic cells. All secreted proteins and proteins that reside in secretory compartments translocate as nascent peptide chains into the ER, where they may undergo folding, modification and assembly before assuming their functional conformations. The ER maintains a specialized oxidizing environment to aid ch...

yeasts have rewired many regulatory networks, such that processes as diverse as ribosomal protein gene regulation, galactose metabolism and mating-type switching, which appear to be very similar at the physiological level, are regulated by different transcription factors that bind to different regulatory sequences. Despite its evolutionary distance to S. cerevisiae being relatively short, C alb...

The endoplasmic reticulum (ER) is a principal site for folding and maturation of transmembrane, secretory and ERresident proteins. Perturbations that alter ER homeostasis can lead to accumulation of unfolded proteins (UPs), which is a threat to all living cells. To cope with the stress, cells activate an intracellular signaling pathway – the unfolded protein response (UPR). The UPR is an integr...

The unfolded protein response is the mechanism by which cells control endoplasmic reticulum (ER) homeostasis. Under normal conditions, UPR not activated; however, under certain stresses, such as hypoxia or altered glycosylation, can be activated due to an accumulation of proteins. activation involves three signaling pathways, IRE1, PERK and ATF6, all play vital roles in returning homeostasis le...

Clonal expansion of mtDNA deletions compromises mitochondrial function in human disease and aging, but how deleterious mtDNA genomes propagate has remained unclear. In this issue (Gitschlag et al., 2016) and in a recent Nature publication, C. elegans studies implicate the mitochondrial unfolded protein response (UPR(mt)) and offer mechanistic insights into this process.