Mitophagy and the release of inflammatory cytokines

NLRP3 Inflammasome and Inflammatory Diseases

“…In autophagy-deficient cells, including autophagic protein depletion [89], activation of the inflammatory NLRP3 complex is enhanced due to mitochondrial dysfunction such as excessive mitochondrial ROS production and changes in mitochondrial membrane permeability [90], contributed to IL-1β and IL-18 secretion. Loss of autophagy/mitophagy can lead to a buildup of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signaling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, and IL-18 [91]. In addition, mitophagy can clear damage mitochondria through a variety of mechanisms, including activation of the PINK/PARKIN pathway [91], p62 aggregation [92], and SESN2 activation [91], thereby preventing excessive inflammation activation.…”

“…Loss of autophagy/mitophagy can lead to a buildup of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signaling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, and IL-18 [91]. In addition, mitophagy can clear damage mitochondria through a variety of mechanisms, including activation of the PINK/PARKIN pathway [91], p62 aggregation [92], and SESN2 activation [91], thereby preventing excessive inflammation activation. Research has shown that resveratrol inhibits NLRP3 activation in macrophages by inhibiting mitochondrial damage and enhancing autophagy [93].…”

“…In neuritis, the neuroinflammation promoted by NLRP3 inflammatory complexes may be amplified and regulated by a glia maturation factor, thus inhibiting the clearance of the protein aggregates that formed as a result of the 3 Oxidative Medicine and Cellular Longevity autophagic pathway [96]. In nonalcoholic steatohepatitis, NLRP3 and caspase-1 can inhibit autophagy by regulating the PINK/PARKIN pathway [91]. Additionally, the NLRP3 inflammasome inhibitor MCC950 can activate autophagy and PPARα through mTOR inhibition [97].…”

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

“…Moreover, releasing of a large amount of certain proteins, such as IL‐1β and IL‐18, 14 from cytosol to extracellular are also considerable evidence of pyroptotic cells. Mitochondrial dysfunction and reactive oxygen species (ROS) production are also associated with macrophage inflammasome activation, which may directly cause cellular damage, oxidative stress, and pyroptotic process 15,16 . Although accumulating evidence demonstrate significant role of inflammasome signaling and pyroptosis in inflammatory diseases, it remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death.…”

Mitochondrial fidelity and metabolic agility control immune cell fate and function

“…The recycling of complete or damaged components of mitochondria occurs in isolation (mitophagy) or as a component of broader recycling of cellular content (macroautophagy/autophagy) to maintain mitochondrial quality control. The molecular machinery governing both mitophagy and autophagy is well defined, and the molecular or pharmacologic disruption of these programs demonstrates their link to innate immunity (129). The genetic depletion of autophagy mediators disrupts autophagy and mitophagy with subsequent extrusion of mtDNA into the cytosol.…”