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