Role of Mitochondria in the Redox Signaling Network and Its Outcomes in High Impact Inflammatory Syndromes

MAGNANI, NATALIA D.; MARCHINI, TIMOTEO; CALABRÓ, VALERIA; ALVAREZ, SILVIA; EVELSON, PABLO

Frontiers in Endocrinology

Frontiers

Lugar: Lausanne; Año: 2020 vol. 11 p. 1 - 15

Inflammation is associated with the release of soluble mediators that drive cellularactivation and migration of inflammatory leukocytes to the site of injury, together withendothelial expression of adhesion molecules, and increased vascular permeability. It isa stepwise tightly regulated process that has been evolved to cope with a wide range ofdifferent inflammatory stimuli. However, under certain physiopathological conditions, theinflammatory response overwhelms local regulatory mechanisms and leads to systemicinflammation that, in turn, might affect metabolism in distant tissues and organs. In thissense, as mitochondria are able to perceive signals of inflammation is one of the firstorganelles to be affected by a dysregulation in the systemic inflammatory response,it has been associated with the progression of the physiopathological mechanisms.Mitochondria are also an important source of ROS (reactive oxygen species) withinmost mammalian cells and are therefore highly involved in oxidative stress. ROSproduction might contribute to mitochondrial damage in a range of pathologies and isalso important in a complex redox signaling network from the organelle to the rest ofthe cell. Therefore, a role for ROS generated by mitochondria in regulating inflammatorysignaling was postulated and mitochondria have been implicated in multiple aspectsof the inflammatory response. An inflammatory condition that affects mitochondrialfunction in different organs is the exposure to air particulate matter (PM). Both afteracute and chronic pollutants exposure, PM uptake by alveolar macrophages havebeen described to induce local cell activation and recruitment, cytokine release, andpulmonary inflammation. Afterwards, inflammatory mediators have been shown to beable to reach the bloodstream and induce a systemic response that affects metabolismin distant organs different from the lung. In this proinflammatory environment, impairedmitochondrial function that leads to bioenergetic dysfunction and enhanced productionof oxidants have been shown to affect tissue homeostasis and organ function. In thepresent review, we aim to discuss the latest insights into the cellular and molecularmechanisms that link systemic inflammation and mitochondrial dysfunction in differentorgans, taking the exposure to air pollutants as a case model.