Mitochondrial stress: Balancing friend and foe

03.03.2014

Runkel ED, Baumeister R, Schulze E.

Exp Gerontol. 2014 Aug;56C:194-201

Exp Gerontol.         online article

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 (UPRmt) is a response of the cell to mitochondrial damage. The transcription factor ATFS-1 triggers UPRmt effector gene expression in the nucleus. The selective exclusion of ATFS-1 from mitochondrial import by stress-induced alterations of the mitochondrialmembrane potential is currently discussed as key activation mechanism. Surprisingly, UPRmt activation often coincideswith a lifespan extension
in Caenorhabditis elegans and the same has recently been reported for mammalian cells. This review summarizes the current model of the UPRmt, 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.