Figure 3.

Mitochondrial stress and mtROS in the inflammatory response. Mitochondrial dysfunction including mtROS generation, reduced ATP synthesis and glutathione levels, and mtDNA release into the cytosol may all lead to mitochondrial stress. Cytoplasmic mtDNA can stimulate type I IFN responses via the cGAS-STING-IRF3 pathway and activate NLRP3 inflammasome and TLR9 pathway to increase proinflammatory cytokines production. mtROS production has been shown to cause DNA damage, unfolded protein response (UPR), and inflammatory responses through HIF-1α and MAPK/NF-κB pathways in LPS-stimulated macrophages.