Many mitochondrial diseases are provoked by structural and functional changes in the complex I. Therefore, the major aim of the studies, T. Yagi’s team conducts, is to develop a therapy for compensation of the complex I defect. The most promising method is transfection with NADH gene of yeasts (Saccharomyces cerevisiae). That gene consist of one subunit (Ndi1) responsible for the NADH to ubiquinone-10 (UQ10) electron transfer in the mammalian mitochondria. Using complex I-deficient Chinese hamster CCL16-B2 mutant cell lines, the researchers from T. Yagi’s laboratory performed successful transfection of those cells’ mitochondria with the Ndi1 gene. The Ndi1-transfected cells with functionally active NADH dehydrogenase, as well as the healthy cells (control with the intact complex I gene) showed electron transfer when malate plus glutamate were employed as respiratory substrates. So, thansfection with Ndi1 gene opens new possibilities in the treatment of mitochondrial diseases with the use of gene therapy.
Place of employment — The Scripps Research Institute Division of Biochemistry, USA.
Contacts — 10550 N. Torrey Pines Rd. La Jolla, CA 92037, USA(858) 784-1000yagi@scripps.edu .
Publications — Molecular remedy of complex I defects: rotenone-insensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae mitochondria restores the NADH oxidase activity of complex I-deficient mammalian cells. Seo BB, Kitajima-Ihara T, Chan EK, Scheffler IE, Matsuno-Yagi A, Yagi T.Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9167–71. Use of the NADH-quinone oxidoreductase (NDI1) gene of Saccharomyces cerevisiae as a possible cure for complex I defects in human cells. Seo BB, Wang J, Flotte TR, Yagi T, Matsuno-Yagi A. J Biol Chem. 2000 Dec 1;275(48):37774–8.
