Abstract
Human NADH dehydrogenase (ubiquinone) Fe-S protein 7 (NDUFS7), participating in the process of oxidative phosphorylation (OXPHOS), is one of the most conserved core subunits of mitochondrial complex I. In addition to containing a mitochondrial targeting sequence (MTS), a functional nuclear localization signal (NLS) and a nuclear export signal (NES) are both demonstrated to be present in NDUFS7. Deficiency of NDUFS7 is associated with Leigh syndrome (LS) and patients suffering from this disease develop movement disorders and other serious complications. Thus, clearing out the controlling mechanism of NDUFS7 subcellular distribution and its functions at the molecular level is important. Previous studies conducted in our laboratory indicated that NDUFS7 could be located in mitochondria, the cytosol and the nucleus. However, the mechanism of regulating its localization is still unknown. Post–translational modifications are well recognized as the candidates for controlling protein localization and functions. The main purpose of this project is to study the influence of phosphorylation on the subcellular localization of NDUFS7 and/or its involvement in the regulation of NDUFS7 functions. The current results showed that the precursor form of NDUFS7 is phosphorylated at tyrosine residues and enhanced by ATP treatment. In addition, the tyrosine phosphorylation of NDUFS7 could be enhanced by c-Src kinase both in vivo and in vitro. However, the subcellular localization of NDUFS7 is not significantly affected by the expression of c-Src as compared to that of the control groups. Moreover, one of the sites involved in the phosphorylation of NDUFS7 is identified to be tyrosine-160, and the stability of NDUFS7 protein is positively regulated by phosphorylation at this residue. Further studies are on the way to explore the effect of NDUFS7 phosphorylation on mitochondrial functions.