STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization.

Although it is reported that mitochondria-localized nuclear transcription factors (TFs) regulate mitochondrial processes such as apoptosis and mitochondrial transcription/respiration, the functions and mechanisms of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs are yet to be fully characterized. Here, we identify STAT6 as a mitochondrial protein that is localized in the outer membrane of mitochondria (OMM). STAT6 in OMM inhibits mitochondrial fusion by blocking MFN2 dimerization. This implies that STAT6 has a critical role in mitochondrial dynamics. Moreover, mitochondrial accumulation of STAT6 in response to hypoxic conditions reveals that STAT6 is a regulator of mitochondrial processes including fusion/fission mechanisms.