Abstract
Numerous physiological and pathological roles have been attributed to the formation of mitochondrial reactive oxygen species (ROS). However, the individual contribution of different mitochondrial processes independently of bioenergetics remains elusive and clinical treatments unavailable. A notable exception to this complexity is found in the case of monoamine oxidases (MAOs). Unlike other ROS-producing enzymes, especially within mitochondria, MAOs possess a distinct combination of defined molecular structure, substrate specificity, and clinically accessible inhibitors. Another significant aspect of MAO activity is the simultaneous generation of hydrogen peroxide alongside highly reactive aldehydes and ammonia. These three products synergistically impair mitochondrial function at various levels, ultimately jeopardizing cellular metabolic integrity and viability. This pathological condition arises from exacerbated MAO activity, observed in many cardiovascular diseases, thus justifying the exploration of MAO inhibitors as effective cardioprotective strategy. In this context, we not only summarize the deleterious roles of MAOs in cardiac pathologies and the positive effects resulting from genetic or pharmacological MAO inhibition, but also discuss recent findings that expand our understanding on the role of MAO in gene expression and cardiac development.