Mitochondrial stress: Balancing friend and foe

Fission-fusion Mitochondria are vital organelles of the aerobic eukaryotic cell. Their dysfunction associates with aging and widespread age-related diseases. To sustain mitochondrial integrity, the cell executes a distinct set of stress-induced protective responses. The mitochondrial unfolded protein response (UPR mt ) is a response of the cell to mitochondrial damage. The transcription factor ATFS-1 triggers UPR mt effector gene expression in the nucleus. The selective exclusion of ATFS-1 from mitochondrial import by stress-induced alterations of the mitochondrial membrane potential is currently discussed as key activation mechanism. Surprisingly, UPR mt activation often coincides with a lifespan extension in Caenorhabditis elegans and the same has recently been reported for mammalian cells. This review summarizes the current model of the UPR mt , its inducers, and its crosstalk with other cellular stress responses. It focuses on the role of mitochondrial function as a regulator of aging and longevity