Figure 1.

The ER and mitochondrial UPRs. ER stress activates the three arms of the UPR^ER: PERK, IRE1, and ATF6. PERK activation leads to phosphorylation of eIF2α, resulting in a protein translation block and transcription of ATF4 and CHOP. IRE1 splices XBP1 mRNA and a spliced form translocates to the nucleus. ATF6 is spliced in the Golgi and the N-terminal fragment acts as a transcription factor. All three arms initiate the transcription of ER-related molecular chaperones and/or folding catalysts. Mitochondrial stress activates the UPR^mt, which consists of ATF5, PERK, and JNK2. During mitochondrial stress, the import of ATF5 into the mitochondria is blocked, leading to the translocation of ATF5 to the nucleus. PERK activation leads to the transcription of ATF4, CHOP, and ATF5. JNK2 binds to the transcription factor c-Jun, which activates the transcription of CHOP. ATF5, PERK and JNK2 all initiate the transcription of mitochondrial proteases, mitochondrial molecular chaperones, and proteins involved in ROS detoxification and mitochondrial import.