scholarly journals Three Classes of Inhibitors Share a Common Binding Domain in Mitochondrial Complex I (NADH:Ubiquinone Oxidoreductase)

1999 ◽  
Vol 274 (5) ◽  
pp. 2625-2630 ◽  
Author(s):  
Jürgen G. Okun ◽  
Peter Lümmen ◽  
Ulrich Brandt
Keyword(s):  
Complex I ◽  
Binding Domain ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex

scholarly journals Paracoccus denitrificans: a genetically tractable model system for studying respiratory complex I

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Owen D. Jarman ◽  
Olivier Biner ◽  
John J. Wright ◽  
Judy Hirst
Keyword(s):  
Complex I ◽  
Paracoccus Denitrificans ◽  
Model System ◽  
Proton Pumping ◽  
Model Systems ◽  
Metabolic Enzyme ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inner Mitochondrial Membrane

AbstractMitochondrial complex I (NADH:ubiquinone oxidoreductase) is a crucial metabolic enzyme that couples the free energy released from NADH oxidation and ubiquinone reduction to the translocation of four protons across the inner mitochondrial membrane, creating the proton motive force for ATP synthesis. The mechanism by which the energy is captured, and the mechanism and pathways of proton pumping, remain elusive despite recent advances in structural knowledge. Progress has been limited by a lack of model systems able to combine functional and structural analyses with targeted mutagenic interrogation throughout the entire complex. Here, we develop and present the α-proteobacterium Paracoccus denitrificans as a suitable bacterial model system for mitochondrial complex I. First, we develop a robust purification protocol to isolate highly active complex I by introducing a His6-tag on the Nqo5 subunit. Then, we optimize the reconstitution of the enzyme into liposomes, demonstrating its proton pumping activity. Finally, we develop a strain of P. denitrificans that is amenable to complex I mutagenesis and create a catalytically inactive variant of the enzyme. Our model provides new opportunities to disentangle the mechanism of complex I by combining mutagenesis in every subunit with established interrogative biophysical measurements on both the soluble and membrane bound enzymes.

scholarly journals Specific features and assembly of the plant mitochondrial complex I revealed by cryo-EM

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Heddy Soufari ◽  
Camila Parrot ◽  
Lauriane Kuhn ◽  
Florent Waltz ◽  
Yaser Hashem
Keyword(s):  
Carbonic Anhydrase ◽  
Complex I ◽  
Mitochondrial Respiratory Chain ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Entry Site ◽  
Lipid Complex ◽  
Maturation Factor ◽  
Specific Complex

Abstract Mitochondria are the powerhouses of eukaryotic cells and the site of essential metabolic reactions. Complex I or NADH:ubiquinone oxidoreductase is the main entry site for electrons into the mitochondrial respiratory chain and constitutes the largest of the respiratory complexes. Its structure and composition vary across eukaryote species. However, high resolution structures are available only for one group of eukaryotes, opisthokonts. In plants, only biochemical studies were carried out, already hinting at the peculiar composition of complex I in the green lineage. Here, we report several cryo-electron microscopy structures of the plant mitochondrial complex I. We describe the structure and composition of the plant respiratory complex I, including the ancestral mitochondrial domain composed of the carbonic anhydrase. We show that the carbonic anhydrase is a heterotrimeric complex with only one conserved active site. This domain is crucial for the overall stability of complex I as well as a peculiar lipid complex composed of cardiolipin and phosphatidylinositols. Moreover, we also describe the structure of one of the plant-specific complex I assembly intermediates, lacking the whole PD module, in presence of the maturation factor GLDH. GLDH prevents the binding of the plant specific P1 protein, responsible for the linkage of the PP to the PD module.

scholarly journals Specific features and assembly of the plant mitochondrial complex I revealed by cryo-EM

2020 ◽  
Author(s):  
Heddy Soufari ◽  
Camila Parrot ◽  
Lauriane Kuhn ◽  
Florent Waltz ◽  
Yaser Hashem
Keyword(s):  
Carbonic Anhydrase ◽  
Complex I ◽  
Mitochondrial Respiratory Chain ◽  
Eukaryotic Cells ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Entry Site ◽  
Lipid Complex ◽  
Additional Domain

AbstractMitochondria are the powerhouses of eukaryotic cells and the site of essential metabolic reactions. Their main purpose is to maintain the high ATP/ADP ratio that is required to fuel the countless biochemical reactions taking place in eukaryotic cells1. This high ATP/ADP ratio is maintained through oxidative phosphorylation (OXPHOS). Complex I or NADH:ubiquinone oxidoreductase is the main entry site for electrons into the mitochondrial respiratory chain and constitutes the largest of the respiratory complexes2. Its structure and composition varies across eukaryotes species. However, high resolution structures are available only for one group of eukaryotes, opisthokonts3–6. In plants, only biochemical studies were carried out, already hinting the peculiar composition of complex I in the green lineage. Here, we report several cryo-electron microscopy structures of the plant mitochondrial complex I at near-atomic resolution. We describe the structure and composition of the plant complex I including the plant-specific additional domain composed by carbonic anhydrase proteins. We show that the carbonic anhydrase is an heterotrimeric complex with only one conserved active site. This domain is crucial for the overall stability of complex I as well as a peculiar lipid complex composed cardiolipin and phosphatidylinositols. Moreover we also describe the structure of one of the plant-specific complex I assembly intermediate, lacking the whole PD module, in presence of the maturation factor GLDH. GLDH prevents the binding of the plant specific P1 protein, responsible for the linkage of the PP to the PD module. Finally, as the carbonic anhydrase domain is likely to be associated with complex I from numerous other known eukaryotes, we propose that our structure unveils an ancestral-like organization of mitochondrial complex I.

scholarly journals GRIM-19, a Cell Death Regulatory Protein, Is Essential for Assembly and Function of Mitochondrial Complex I

2004 ◽  
Vol 24 (19) ◽  
pp. 8447-8456 ◽  
Author(s):  
Guochang Huang ◽  
Hao Lu ◽  
Aijun Hao ◽  
Dominic C. H. Ng ◽  
Sathivel Ponniah ◽  
...  
Keyword(s):  
Cell Death ◽  
Electron Transfer ◽  
Complex I ◽  
Cellular Localization ◽  
Regulatory Protein ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Native Form

ABSTRACT Mitochondria play essential roles in cellular energy production via the oxidative phosphorylation system (OXPHOS) consisting of five multiprotein complexes and also in the initiation of apoptosis. NADH:ubiquinone oxidoreductase (complex I) is the largest complex that catalyzes the first step of electron transfer in the OXPHOS system. GRIM-19 was originally identified as a nuclear protein with apoptotic nature in interferon (IFN)- and all-trans-retinoic acid (RA)-induced tumor cells. To reveal its biological role, we generated mice deficient in GRIM-19 by gene targeting. Homologous deletion of GRIM-19 causes embryonic lethality at embryonic day 9.5. GRIM-19−/− blastocysts show retarded growth in vitro and, strikingly, display abnormal mitochondrial structure, morphology, and cellular distribution. We reexamined the cellular localization of GRIM-19 in various cell types and found its primary localization in the mitochondria. Furthermore, GRIM-19 is detected in the native form of mitochondrial complex I. Finally, we show that elimination of GRIM-19 destroys the assembly and electron transfer activity of complex I and also influences the other complexes in the mitochondrial respiratory chain. Our result demonstrates that GRIM-19, a gene product with a specific role in IFN-RA-induced cell death, is a functional component of mitochondrial complex I and is essential for early embryonic development.

The ND1 Subunit Constructs the Inhibitor Binding Domain in Bovine Heart Mitochondrial Complex I†

Biochemistry ◽  
2007 ◽  
Vol 46 (21) ◽  
pp. 6409-6416 ◽  
Author(s):  
Masatoshi Murai ◽  
Atsushi Ishihara ◽  
Takaaki Nishioka ◽  
Takao Yagi ◽  
Hideto Miyoshi
Keyword(s):  
Complex I ◽  
Binding Domain ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inhibitor Binding ◽  
Bovine Heart

scholarly journals A scaffold of accessory subunits links the peripheral arm and the distal proton-pumping module of mitochondrial complex I

2011 ◽  
Vol 437 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Heike Angerer ◽  
Klaus Zwicker ◽  
Zibiernisha Wumaier ◽  
Lucie Sokolova ◽  
Heinrich Heide ◽  
...  
Keyword(s):  
Complex I ◽  
Structural Information ◽  
Proton Pumping ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Central Function ◽  
Membrane Protein Complex ◽  
Accessory Subunits ◽  
Insight Into

Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a very large membrane protein complex with a central function in energy metabolism. Complex I from the aerobic yeast Yarrowia lipolytica comprises 14 central subunits that harbour the bioenergetic core functions and at least 28 accessory subunits. Despite progress in structure determination, the position of individual accessory subunits in the enzyme complex remains largely unknown. Proteomic analysis of subcomplex Iδ revealed that it lacked eleven subunits, including the central subunits ND1 and ND3 forming the interface between the peripheral and the membrane arm in bacterial complex I. This unexpected observation provided insight into the structural organization of the connection between the two major parts of mitochondrial complex I. Combining recent structural information, biochemical evidence on the assignment of individual subunits to the subdomains of complex I and sequence-based predictions for the targeting of subunits to different mitochondrial compartments, we derived a model for the arrangement of the subunits in the membrane arm of mitochondrial complex I.

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