ATF5 contains both a nuclear localization sequence and a mitochondrial targeting sequence (Fiorese et al. 2016). In unstressed cells, ATF5 is efficiently imported into mitochondria, where it is likely degraded by LONP1 (Fiorese et al. 2016). Upon mitochondrial stress that causes a reduction in mitochondrial import of proteins, less ATF5 is imported into mitochondria, ATF5 accumulates in the cytosol, and a greater amount of ATF5 is imported into the nucleus (Fiorese et al. 2016). Within the nucleus ATF5, activates transcription of genes such as HSPA9 (mtHSP70), HSPE1 (HSP10, Chaperonin 10), LONP1 (Fiorese et al. 2016), and possibly CHOP (Yamazaki et al. 2010) that alleviate mitochondrial stress. The action of ATF5 appears to be downstream of the activation of HSF1 (Sutandy et al. 2023).