FIGURE 2.

Activation of the mitochondrial unfolded protein response (UPR^mt). The UPR^mt is activated when there is an excess of misfolded proteins within the organelle. The UPR^mt transcriptional regulator ATF5 (ATFS-1 in yeast) contains both a mitochondrial targeting sequence (MTS) and a nuclear localization signal (NLS). Under normal conditions, ATF5 is imported into mitochondria where it is degraded. However, increased levels of misfolded proteins inside mitochondria lead to abrogation of ATF5 import. Instead, ATF5 translocates to the nucleus where it activates a transcriptional response aimed at restoring mitochondrial health and proteostasis.