Mitochondrial dysfunction and oxidative stress in heart disease

Abstract

Beyond their role as a cellular powerhouse, mitochondria are emerging as integral players in molecular signaling and cell fate determination through reactive oxygen species (ROS). While ROS production has historically been portrayed as an unregulated process driving oxidative stress and disease pathology, contemporary studies reveal that ROS also facilitate normal physiology. Mitochondria are especially abundant in cardiac tissue; hence, mitochondrial dysregulation and ROS production are thought to contribute significantly to cardiac pathology. Moreover, there is growing appreciation that medical therapies designed to mediate mitochondrial ROS production can be important strategies to ameliorate cardiac disease. In this review, we highlight evidence from animal models that illustrates the strong connections between mitochondrial ROS and cardiac disease, discuss advancements in the development of mitochondria-targeted antioxidant therapies, and identify challenges faced in bringing such therapies into the clinic.

Heart disease: Signaling a halt to disease progression

Heart disease progression could be tackled by targeting signaling molecules that cause oxidative stress. Jennifer Kwong at Emory University School of Medicine in Atlanta, USA, and co-workers reviewed research into the role of mitochondria and their associated signaling molecules in the development of heart disease. Mitochondria are a major source of reactive oxygen species (ROS), signaling molecules involved in muscle contraction and calcium transfer in the heart, but they also destroy ROS to maintain a balance. Disruption to this balance can lead to elevated ROS, causing DNA and cellular damage, triggering disease. Animal trials using drugs to target mitochondrial ROS show promise in limiting heart disease progression. Further research is needed to determine whether this approach will work in humans and which specific heart problems might benefit from such therapies.