Figure 7.
Activation of the JAK-STAT pathway by viruses and the biogenesis, fission and fusion life cycle of mitochondria. Viral infections activate a cascade of signals to produce cytokines, which then activate JAK-STAT proteins which then form a complex and translocate into the nucleus. The STAT1/2 dimer protein complex binds to IRF9 in the nucleus and the resulting trimer interacts with DNA at transcription factor binding sites, and upregulates gene expression. The dotted red line indicates effects of STAT2 on mitochondrial fission, mediated by DRP1 phosphorylation in healthy cells. Mitochondrial morphology is maintained by a balance of fission and fusion events, with disparity leading to a distinct shift in viability of the organelle, which can result in disease states. Phosphorylation of DRP1 at differing serine residues (Ser616 and Ser637) within the protein results in varied effects on DRP1 activity. Phosphorylation at Ser637 inhibits the GTPase activity of DRP1, leading to a defect in mitochondrial fission—promoting mitochondrial elongation.