Mitochondrial control of inflammation

Lorenzo Galluzzi and colleagues discuss the molecular mechanisms through which mitochondrial dysfunction elicits inflammatory reactions, the cellular pathways that are in place to control them and how the dysregulation of these systems contributes to pathology. Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal of permeabilized mitochondria. However, when the homeostatic capacity of such systems is exceeded or when such systems are defective, inflammatory reactions elicited by mitochondria can become pathogenic and contribute to the aetiology of human disorders linked to autoreactivity. In addition, inefficient inflammatory pathways induced by mitochondrial DAMPs can be pathogenic as they enable the establishment or progression of infectious and neoplastic disorders. Here we discuss the molecular mechanisms through which mitochondria control inflammatory responses, the cellular pathways that are in place to control mitochondria-driven inflammation and the pathological consequences of dysregulated inflammatory reactions elicited by mitochondrial DAMPs.

Automated summary

This article discusses the molecular mechanisms by which mitochondrial dysfunction leads to inflammatory reactions, the cellular pathways that regulate them, and the pathological consequences of dysregulated inflammatory responses elicited by mitochondrial damage-associated molecular patterns (DAMPs).