From discovery of the CHOP axis and targeting ClpP to the identification of additional axes of the UPRmt driven by the estrogen receptor and SIRT3

The mitochondrial UPR (UPR^mt) is rapidly gaining attention. While most studies on the UPR^mt have focused on its role in aging, emerging studies suggest an important role of the UPR^mt in cancer. Further, several of the players of the UPR^mt in mammalian cells have well reported roles in the maintenance of the organelle. The goal of this review is to emphasize aspects of the UPR^mt that have been overlooked in the current literature, describe the role of specific players of the UPR^mt in the biology of the mitochondria and highlight the intriguing possibility that targeting the UPR^mt in cancer may be already within reach.