Cross talk between SOD1 and the mitochondrial UPR in cancer and neurodegeneration

The mitochondrial unfolded protein response (UPRmt) is rapidly gaining attention. While the CHOP (ATF4/5) axis of the UPRmt was the first to be described, other axes have subsequently been reported. Validation of this complex pathway in C. elegans has been extensively studied. However, validation of the UPRmt in mouse models of disease known to implicate mitochondrial reprogramming or dysfunction, such as cancer and neurodegeneration, respectively, is only beginning to emerge. This review summarizes recent findings and highlights the major role of the superoxide dismutase SOD1 in the communication between the mitochondria and the nucleus in these settings. While SOD1 has mostly been studied in the context of familial amyotrophic lateral sclerosis (fALS), recent studies suggest that SOD1 may be a potentially important mediator of the UPRmt and converge to emphasize an increasingly vital role of SOD1 as a therapeutic target in cancer.