Fig. 3

Hypothetical model of the mitochondrial unfolded protein response (UPR^mt) signaling in cancer. Mitochondrial dysfunction increases mtROS (oxidative stress), which damages proteins in the mitochondria and cause the unfolding and aggregation of mitochondrial proteins (proteotoxic stress). In response, the transcription factor ATF5 induces the upregulation of mitochondrial components to ease proteotoxic stress. Chaperones HSP60, HSP10, and mtHSP70 mediate the refolding of proteins into their proper conformation. Proteases LONP1 and ClpP cleave and dispose of any additional damaged proteins that did not undergo processing by HSPs. Together, this system maintains mitochondrial integrity in the face of continuous oxidative and proteotoxic stress in cancer