Redox signaling in the cardiomyocyte: From physiology to failure

• The view that ROS are either harmful or beneficial is very simplistic.
• ROS can mediate specific post-translational modifications of biomolecules involved in intracellular signaling networks.
• Redox signaling involves spatially and temporally confined ROS production which modulates activity of signaling molecules.
• The NADPH oxidase proteins Nox2 and Nox4 are major enzymatic sources of ROS involved in cell signaling in cardiomyocytes.
• Redox signaling in the heart is involved in acute and chronic cardiac adaptations to diverse stresses.

The specific effect of oxygen and reactive oxygen species (ROS) in mediating post-translational modification of protein targets has emerged as a key mechanism regulating signaling components, a process termed redox signaling. ROS act in the post-translational modification of multiple target proteins including receptors, kinases, phosphatases, ion channels and transcription factors. Both O2 and ROS are major source of electrons in redox reactions in aerobic organisms. Because the heart has the highest O2 consumption among body organs, it is not surprising that redox signaling is central to heart function and pathophysiology. In this article, we review some of the main cardiac redox signaling pathways and their roles in the cardiomyocyte and in heart failure, with particular focus on the specific molecular targets of ROS in the heart.