CORE at the boundary of stress resistance and longevity.

As chronological age of an organism increases, a number of errors accumulate at different levels of biological organization. The tendency of errors to accumulate and cause downstream problems in maintenance of cellular homeostasis is met by numerous protection and repair mechanisms. Maintenance of proteins is vital for cell viability and longevity, thus cellular proteostasis is supported by chaperone networks in every cellular compartment, as well as other pathways ensuring timely chaperone expression and activity. In this minireview, we summarize the progress related to the cross-organelle stress response (CORE), in charge of orchestrating a cell-wide response to compartmentalized proteotoxicity. The proposed CORE pathway encompasses activation of protein conformational maintenance machineries, antioxidant enzymes and metabolic changes simultaneously in the cytosol, mitochondria and the ER. We discuss its importance in cell survival and longevity as well as its potential to serve as a pharmaceutical target in age-related diseases.