Mitochondrial interferon-induced transmembrane protein-1 is a critical regulator of cell death in MPRO cells

Interferon-induced transmembrane protein 1 (IFITM1) is a transmembrane protein that is an essential mediator of interferon-induced anti-proliferation. Identifying the functional role of IFITM1 has been difficult because of high expression of the protein induces cell death. In this study, we showed that IFITM1 is localized to the mitochondria and that its expression is related to mitochondrial reactive oxygen species (mROS). Overexpression of IFITM1 resulted in a wrinkled and ruptured cell morphology, and subcellular fractionation revealed IFITM1 expression in the mitochondria and the plasma membrane. Interestingly, IFITM1 was expressed at high levels in the mitochondria of MPRO cells, but only at low levels in the plasma membrane. A mitochondrial staining assay confirmed that IFITM1 was localized to the mitochondria in MPRO cells. In addition, IFITM1 expression was significantly increased by treatment with H2O2, arachidonic acid, and dithiothreitol. These findings suggest that IFITM1 expression is not restricted to the membrane, but is present in the mitochondria as well. Furthermore, mitochondrial IFITM1 expression is regulated by mROS.