Evolutionary Comeuppance: Mitochondrial Stress Awakens the Remnants of Ancient Bacterial Warfare

Mitochondria are organelles descended from an endosymbiosed bacterium, and many bacterial toxins impair mitochondria, likely as an echo of ancient bacterial warfare. However, the signal transduction pathways that translate mitochondrial dysfunction into a transcriptional program for detoxification have not been well understood. In this issue of Cell Metabolism , Mao et al. (2019) provide insight into how mitochondrial perturbations can activate both the mitochondrial unfolded protein response (UPR mito ) and detoxification response and, importantly, how these responses differentially affect organismal physiology under normal conditions or with pathogenic challenges.