Mitochondria as a centrally positioned hub in the innate immune response

Abstract

Mitochondria are vital organelles involved in numerous cellular functions ranging from energy metabolism to cell survival. Emerging evidence suggests that mitochondria provide a platform for signaling pathways involved in innate immune response. Mitochondrial ROS (mtROS) production, mitochondrial DNA (mtDNA) release, mitochondrial antiviral signaling protein (MAVS) are key triggers in the activation of innate immune response following variety of stress signals that include infection, tissue damage and metabolic dysregulation. The process is mediated through pattern recognition receptors (PRRs) that consist of retinoic acid inducible gene like receptors (RLRs), c-type lectin receptors (CLRs), toll type receptors (TLRs) and nuclear oligomerization-domain like receptors (NLRs). These signals converge to form a multiprotein complex called inflammasome that leads to caspase-1 activation to promote processing of precursor cytokines (pro-IL1β and pro-IL-18) to active cytokines (IL-1β and IL-18). It appears that mitochondria induced inflammasome activation contributes to inflammatory process in many diverse disorders. Therefore, strategies aimed at modulating mitochondria mediated inflammasome activation might be beneficial in many pathophysiological conditions. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

Keywords: Inflammasome: innate immune response; Inflammation; Mitochondria; NLRP3.