xenotransplantation of mitochondrial electron transfer enzyme, ndi1, in myocardial reperfusion injury异种移植的线粒体电子转移酶,ndi1心肌再灌注损伤.pdfVIP

Xenotransplantation of Mitochondrial Electron Transfer Enzyme, Ndi1, in Myocardial Reperfusion Injury 1,2 2 2 2 2 Cynthia N. Perry , Chengqun Huang , Wayne Liu , Najib Magee , Raquel Sousa Carreira , Roberta A. Gottlieb2* 1 Department of Pathology, University of California San Diego School of Medicine, La Jolla, California, United States of America, 2 SDSU Bioscience Center, San Diego, California, United States of America Abstract A significant consequence of ischemia/reperfusion (I/R) is mitochondrial respiratory dysfunction, leading to energetic deficits and cellular toxicity from reactive oxygen species (ROS). Mammalian complex I, a NADH-quinone oxidoreductase enzyme, is a multiple subunit enzyme that oxidizes NADH and pumps protons across the inner membrane. Damage to complex I leads to superoxide production which further damages complex I as well as other proteins, lipids and mtDNA. The yeast, S. cerevisiae, expresses internal rotenone insensitive NADH-quinone oxidoreductase (Ndi1); a single 56kDa polypeptide which, like the multi-subunit mammalian complex I, serves as the entry site of electrons to the respiratory chain, but without proton pumping. Heterologous expression of Ndi1 in mammalian cells results in protein localization to the inner mitochondrial membrane which can function in parallel with endogenous complex I to oxidize NADH and pass electrons to ubiquinone. Expression of Ndi1 in HL-1 cardiomyocytes and in neonatal rat ventricular myocytes protected the cells