Figure 1.

Activation of the mitochondrial unfolded protein response in C. elegans. Under normal conditions, ATFS-1 is brought into the mitochondria and undergoes disassembly due to the action of LONP-1. However, when ATFS-1 transport is blocked in cases such as homeostasis disturbance, hypoxia, and ETC dysfunction, it accumulates in the perinuclear region and causes activation of the UPRmt. Unfolded proteins are subsequently broken down into polypeptides by CLPP in the mitochondria and then transported out of the mitochondria by the HAF1 transporter to activate the UBL5 and DEV1 transcriptional complex factors. Under stress situations, UPRmt is activated as a result of UBL5 and DEV1 redistribution and chromatin reorganization, which is the consequence of LIN65 translocation from the cytoplasm to the perinuclear area due to MET2 action. Activation of the UPRmt produces a series of biological changes toward restoring mitochondrial function.