Figure 2
The ATFS-1-mediated mitochondrial unfolded protein response. The UPRmt is a protective transcriptional response to the accumulation of unfolded proteins or respiratory chain dysfunction that promotes adaptation and survival during mitochondrial dysfunction. Cells utilize the transcription factor ATFS-1 to monitor mitochondrial function and adjust transcription accordingly. Like PINK1, ATFS-1 is imported into mitochondria and quickly degraded in healthy cells, but accumulates in the cytosol during mitochondrial stress due to respiratory chain dysfunction, unfolded protein accumulation or high levels of reactive oxygen species, when mitochondrial import efficiency is impaired. Because ATFS-1 has a nuclear localization sequence (NLS), as well as its mitochondrial localization sequence (MTS), this causes it to localize to the nucleus, where it induces the transcription of genes involved in mitochondrial protein homeostasis, reactive oxygen species (ROS) and small molecule detoxification, glycolysis, and innate immunity.