FIGURE 3.

Mitochondrial ROS surveillance pathways. Three ROS‐responsive pathways are illustrated, from left to right. First, the ESRE pathway, which is triggered by superoxide, involves multiple transcription factors, the PBAF chromatin remodeling complex, and JMJC‐1 to regulate the expression of ESRE genes (i.e., genes with the 11‐nucleotide TCTGCGTCTCT motif in their promoter region). Abnormal buildup of reducing equivalents (due to mitochondrial disruption) that paradoxically increases ROS production can also activate the ESRE pathway. Second, ROS accumulation induces GCN‐2‐dependent eIF2ɑ phosphorylation, altering translational profile, and working in concert with the UPR^mt transcription factor ATFS‐1/ATF5 to restore proteostasis. Third, oxidative stress triggers Vms1 of the MAD pathway, to translocate from the cytosol to the OMM. Once there, it recruits the ribosomal quality control complex to help release proteins whose translocation has stalled for proteasomal degradation. Abbreviations: IMM—Inner mitochondrial membrane, OMM—outer mitochondrial membrane, ROS—reactive oxygen species, TOM/TIM—translocase of the outer/inner membrane