...Leonid A. Sazanov My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally...

...Edwin T. Gibbs, II; Chad A. Lerner; Mark A. Watson; Hoi-Shan Wong; Akos A. Gerencser; Martin D. Brand Superoxide/hydrogen peroxide production by site I Q in complex I of the electron transport chain is conventionally assayed during reverse electron transport (RET) from ubiquinol to NAD. However...

... to complex I inhibition, but the mechanism by which metformin leads to complex I inhibition is not fully understood. Although it has been reported that the incubation of functionally isolated complex I in the presence of high concentrations of metformin led to its inhibition, much lower concentrations...

...Hannah R. Bridges; Andrew J. Y. Jones; Michael N. Pollak; Judy Hirst The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause...

..., stabilized mitochondrial membrane potential and decreased production of H 2 O 2 in mitochondria. High-resolution respirometry in permeabilized cells combined with native PAGE demonstrated that Nox4 specifically inhibits the activity of mitochondrial electron transport chain complex I, and this was associated...

...Hannah R. Bridges; Ljuban Grgic; Michael E. Harbour; Judy Hirst NADH:ubiquinone oxidoreductase (complex I) is an entry point for electrons into the respiratory chain in many eukaryotes. It couples NADH oxidation and ubiquinone reduction to proton translocation across the mitochondrial inner...

... between them. Two modes of operation by isolated mitochondria result in significant O 2 •− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD...

... understood. Previous studies in purified mitochondria have found that the highest rates of superoxide production are observed with succinate-driven reverse-electron transfer through complex I, although the physiological importance of this pathway is disputed because it necessitates high concentrations...

... of NO • to the Cu B /haem-a 3 site in mitochondrial complex IV, it has been proposed by several laboratories that complex I can be inhibited by S-nitrosation of a cysteine. However, direct molecular evidence for this is lacking. In this investigation we have combined separation techniques for complex I (blue-native...

..., under optimal conditions, especially complex I-mediated NADH oxidation in AlaM-treated mitochondria was much higher than what has been previously measured by other techniques. Our results also show a difference in substrate specificities for complex I in mitochondria as compared with inside-out...

... by rotenone, an inhibitor of the proton-pumping complex I, when matrix-generated NADH is used as substrate. Although no effects of the NDI1 defect on vegetative growth and sexual differentiation were observed, the germination of both sexual and asexual ndi1 mutant spores is significantly delayed. Crosses...

...Margarida DUARTE; Helena PÓPULO; Arnaldo VIDEIRA; Thorsten FRIEDRICH; Ulrich SCHULTE We have cloned and inactivated, by repeat-induced point mutations, the nuclear gene encoding the 19.3kDa subunit of complex I (EC 1.6.5.3) from Neurospora crassa , the homologue of the bovine PSST polypeptide...

... anions, hydrogen peroxide and peroxynitrite, the latter shown by nitration of mitochondrial proteins. Long-term incubation of mitochondrial membranes with NO resulted in a persistent inhibition of NADH:cytochrome c reductase activity, interpreted as inhibition of NADH:ubiquinone reductase (Complex I...

... of respiration which was due to a redox-dependent, progressive inhibition of complex I activity. No other enzyme of the respiratory chain was inhibited in this way. At the same time, we detected a paradoxical removal of oxygen by the extracellular medium. This removal was due to a chemical interaction between...

...Fátima FERREIRINHA; Margarida DUARTE; Ana M. P. MELO; Arnaldo VIDEIRA We have cloned and inactivated in vivo , by repeat-induced point mutations, the nuclear gene encoding a 21 kDa subunit of complex I from Neurospora crassa . Mitochondria from the nuo21 mutant lack this specific protein but retain...