scholarly journals Inhibitors of the Quinone-binding Site Allow Rapid Superoxide Production from Mitochondrial NADH:Ubiquinone Oxidoreductase (Complex I)

2004 ◽  
Vol 279 (38) ◽  
pp. 39414-39420 ◽  
Author(s):  
Adrian J. Lambert ◽  
Martin D. Brand
Keyword(s):  
Binding Site ◽  
Complex I ◽  
Superoxide Production ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Quinone Binding

scholarly journals Accessory NUMM (NDUFS6) subunit harbors a Zn-binding site and is essential for biogenesis of mitochondrial complex I

2015 ◽  
Vol 112 (18) ◽  
pp. 5685-5690 ◽  
Author(s):  
Katarzyna Kmita ◽  
Christophe Wirth ◽  
Judith Warnau ◽  
Sergio Guerrero-Castillo ◽  
Carola Hunte ◽  
...  
Keyword(s):  
Binding Site ◽  
Complex I ◽  
Proton Pumping ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
X Ray Crystallography ◽  
Late Step ◽  
Multistep Process ◽  
Assembly Factor ◽  
Accessory Subunit ◽  
Assembly Intermediate

Mitochondrial proton-pumping NADH:ubiquinone oxidoreductase (respiratory complex I) comprises more than 40 polypeptides and contains eight canonical FeS clusters. The integration of subunits and insertion of cofactors into the nascent complex is a complicated multistep process that is aided by assembly factors. We show that the accessory NUMM subunit of complex I (human NDUFS6) harbors a Zn-binding site and resolve its position by X-ray crystallography. Chromosomal deletion of the NUMM gene or mutation of Zn-binding residues blocked a late step of complex I assembly. An accumulating assembly intermediate lacked accessory subunit N7BM (NDUFA12), whereas a paralog of this subunit, the assembly factor N7BML (NDUFAF2), was found firmly bound instead. EPR spectroscopic analysis and metal content determination after chromatographic purification of the assembly intermediate showed that NUMM is required for insertion or stabilization of FeS cluster N4.

scholarly journals Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I

2013 ◽  
Vol 288 (34) ◽  
pp. 24799-24808 ◽  
Author(s):  
Joe Carroll ◽  
Shujing Ding ◽  
Ian M. Fearnley ◽  
John E. Walker
Keyword(s):  
Binding Site ◽  
Complex I ◽  
Post Translational Modifications ◽  
Quinone Binding

scholarly journals Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane

2004 ◽  
Vol 382 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Adrian J. LAMBERT ◽  
Martin D. BRAND
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Complex I ◽  
Superoxide Production ◽  
Ph Gradient ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Protonmotive Force ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Reverse Electron Transport

The relationship between protonmotive force and superoxide production by mitochondria is poorly understood. To address this issue, the rate of superoxide production from complex I of rat skeletal muscle mitochondria incubated under a variety of conditions was assessed. By far, the largest rate of superoxide production was from mitochondria respiring on succinate; this rate was almost abolished by rotenone or piericidin, indicating that superoxide production from complex I is large under conditions of reverse electron transport. The high rate of superoxide production by complex I could also be abolished by uncoupler, confirming that superoxide production is sensitive to protonmotive force. It was inhibited by nigericin, suggesting that it is more dependent on the pH gradient across the mitochondrial inner membrane than on the membrane potential. These effects were examined in detail, leading to the conclusions that the effect of protonmotive force was mostly direct, and not indirect through changes in the redox state of the ubiquinone pool, and that the production of superoxide by complex I during reverse electron transport was at least 3-fold more sensitive to the pH gradient than to the membrane potential.

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