Analysis of mitochondrial function of STAT3 in mammalian cells exposed to genotoxic stress

STAT3 (Signal Transducer and Activator of Transcription 3) is a nuclear transcription factor involved in many physiological processes such as cell proliferation and survival, and pathological processes such as cancer. Recently, it was reported that there is a pool of mitochondrial STAT3 (mitoSTAT3) of about 5-10% with a role in regulating the mitochondrial gene expression and the activity of the electron transport chain (ETC) and of the mitochondrial permeability transition pore (mPTP), resulting in a reduction of reactive oxygen species (ROS) level and of cell death. Whilst the nuclear function of STAT3 is well described, little is known about non-canonical function of mitoSTAT3. Interesting it is the role of the phosphorylation of serine 727 that seems to be important for its mitochondrial translocation and proper mitochondrial functioning. The aim of this study is to investigate the role of mitoSTAT3 upon genotoxic stress in mammalian cells transduced with lentiviral vectors to stably express mitochondrial STAT3 in its wild-type and mutated forms at serine 727. We performed biological assays of cell proliferation, cell survival, apoptosis induction, and gene expression analysis to investigate the role of mitoSTAT3 in the cells response to genotoxic stress induced by UVC radiation. Our results show a higher proliferation and survival of cells stably expressing mitoSTAT3 in the forms that allow the phosphorylation of serine 727.