FIG. 11.

Schematic diagram depicting ER stress-induced cellular events leading to mitochondrial damage, intracellular Ca²⁺ dysregulation, and contractile dysfunction in the heart as well as how chronic Akt activation may rescue the heart from ER stress-induced cardiac anomalies. TUDCA (an ER chaperon to inhibit ER stress). Please note that intracellular Ca²⁺ overload and dysregulation may occur immediately after induction of ER stress and/or as the final instigator to trigger cardiac contractile dysfunction after onset of mitochondrial damage and ROS production. Also note that ROS production and mitochondrial damage may happen in a reciprocal manner, leading to a vicious cycle for ROS accumulation.