Mitophagy and the release of inflammatory cytokines.

ABSTRACT

Mitophagy is a selective form of autophagy in which damaged or dysfunctional mitochondria are specifically targeted by autophagosomes for lysosomal degradation. Studies have demonstrated that loss of autophagy/mitophagy can lead to a build-up of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signalling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1ß, IL-18, type I IFN and macrophage migration inhibitory factor (MIF). Moreover, release of these cytokines can subsequently promote the release of others, including IL-23 and IL-17. Thus, as well as being essential for normal cell homeostasis and mitochondrial health, mitophagy may represent an important regulatory mechanism controlling inflammatory responses in immune cells. This review discusses our current understanding of the mechanisms through which mitophagy regulates inflammatory cytokine release.