Figure 1.

Regulation of the mitochondrial unfolded protein response (UPR^mt) in C. elegans. The bZIP transcription factor ATFS-1 harbors an amino-terminal MTS and a nuclear localization sequence (NLS) within the bZIP domain near the C-terminus. During cell growth, the majority of ATFS-1 is imported into the mitochondrial matrix via the TIM and TOM translocases and subsequently degraded by the protease LONP. However, if mitochondrial protein import capacity is reduced due to mitochondrial dysfunction or high levels of OXPHOS protein import, ATFS-1 import is impaired, causing it to accumulate in the cytosol and traffic to the nucleus, where it regulates the transcription of over 600 genes that promote mitochondrial proteostasis and biogenesis, glycolysis, ROS detoxication, and innate immunity.