Fig. 6. Proposed mechanisms for causing age-associated heart failure by cardiac-specific mitoNEET downregulation.

The mitoNEET protein is specifically downregulated in the hearts during normal aging. Deletion of mitoNEET primarily causes an impairment of mitochondrial integrity and a mitochondrial iron overload, and enhances ROS production, which secondarily leads to mitochondrial dysfunction. Enhanced ROS production leads to cardiac dysfunction and the development of heart failure, resulting in short life span. ROS, reactive oxygen species.