The association of mitochondria with inflammasome signaling in rpe cells

Abstract

Mitochondria are vital organelles especially in metabolically active retinal pigment epithelium (RPE) cells but in age-related macular degeneration, they are also a source of factors that increase the cell stress. It is well known that excessive amount of reactive oxygen species (ROS) activate NLRP3, a pattern-recognition receptor capable of forming inflammasomes. Inflammasomes are intracellular protein complexes that can result in the activation of two pro-inflammatory cytokines, IL-1beta and/or IL-18, and promote pyroptotic cell death. We have recently shown that mitochondrial DNA (mtDNA), released to the cytosol upon mitochondrial damage, serves also as an activator for inflammasome pathway in human RPE cells. Its receptor is AIM2 that is specialized to respond to double-stranded DNA. Danger signals from dysfunctional mitochondria can activate both inflammasome types in same cells and thereby further enhance the inflammatory response. Collectively, recent data suggest that aged and dysfunctional mitochondria are a major risk factor that contribute to retinal inflammation by promoting the activation of different types of inflammasomes in human RPE cells.