Monoamine oxidases: A missing link between mitochondria and inflammation in chronic diseases ?
Lise Beucher, Claudie Gabillard-Lefort, Olivier R. Baris, Jeanne Mialet‐Perez
Abstract
The role of mitochondria spans from the regulation of the oxidative phosphorylation, cell metabolism and survival/death pathways to a more recently identified function in chronic inflammation. In stress situations, mitochondria release some pro-inflammatory mediators such as ATP, cardiolipin, reactive oxygen species (ROS) or mitochondrial DNA, that are believed to participate in chronic diseases and aging. These mitochondrial Damage-Associated Molecular Patterns (mito-DAMPs) can modulate specific receptors among which TLR9, NLRP3 and cGAS-STING, triggering immune cells activation and sterile inflammation. In order to counter the development of chronic diseases, a better understanding of the underlying mechanisms of low grade inflammation induced by mito-DAMPs is needed. In this context, monoamine oxidases (MAO), the mitochondrial enzymes that degrade catecholamines and serotonin, have recently emerged as potent regulators of chronic inflammation in obesity-related disorders, cardiac diseases, cancer, rheumatoid arthritis and pulmonary diseases. The role of these enzymes in inflammation embraces their action in both immune and non-immune cells, where they regulate monoamines levels and generate toxic ROS and aldehydes, as by-products of enzymatic reaction. Here, we discuss the more recent advances on the role and mechanisms of action of MAOs in chronic inflammatory diseases. Mitochondria has emerged as an important regulator of sterile inflammation in chronic diseases, through the release of pro-inflammatory mediators called mito-DAMPs (Damage-Associated Molecular Patterns). Recently, monoamine oxidases (MAO), the mitochondrial enzymes that degrade catecholamines and serotonin, were described as potent regulators of chronic inflammation in obesity-related disorders, cardiac diseases, cancer, rheumatoid arthritis and pulmonary diseases. The role of these enzymes in inflammation embraces their action in both immune and non-immune cells, where they regulate monoamines levels and generate toxic ROS and aldehydes, as by-products of enzymatic reaction. This review discuss the more recent advances on the role and mechanisms of action of MAOs in chronic inflammatory diseases. • Sterile inflammation underlies the development of chronic diseases such as myocardial infarction, obesity-related disorders, pulmonary obstructive disease, rheumatoid arthritis and cancer, which display increased prevalence in the world due to population aging. • Mitochondrial alterations are believed to participate in the activation of inflammatory pathways through the release of mito-DAMPs (Damage-Associated Molecular Patterns) and the activation of immune cells. • Monoamine oxidase (MAOs) over-activation is a common hallmark of several chronic diseases and increased MAOs activity leads to altered substrate (catecholamines, serotonin) levels and/or accumulation of H 2 O 2 and aldehydes, a cause of mitochondrial damage and oxidative stress. • Recent evidences link MAOs activation and mito-DAMPs to the regulation of immune cells and inflammatory processes in different chronic diseases • The selective MAO inhibitors that are currently in use for neurodegenerative diseases and depression could help to relieve inflammatory processes in peripheral diseases.