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) is rapidly gaining attention. While most studies on the UPR have focused on its role in aging, emerging studies suggest an important role of the UPR in cancer. Further, several of the players of the UPR 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 that have been overlooked in the current literature, describe the role of specific players of the UPR in the biology of the mitochondria and highlight the intriguing possibility that targeting the UPR in cancer may be already within reach.