The Assembly Pathway of Mitochondrial Respiratory Chain Complex I. 2017

Sergio Guerrero-Castillo, and Fabian Baertling, and Daniel Kownatzki, and Hans J Wessels, and Susanne Arnold, and Ulrich Brandt, and Leo Nijtmans
Molecular Bioenergetics Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Cluster of Excellence Frankfurt Macromolecular Complexes, Goethe-University, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Germany.

Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes. We delineate the stepwise incorporation of all but one subunit into a series of distinct assembly intermediates and their association with known and putative assembly factors, which had not been implicated in this process before. The resulting detailed and comprehensive model of complex I assembly is fully consistent with recent structural data and the remarkable modular architecture of this multiprotein complex.

UI MeSH Term Description Entries
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002701 Chloramphenicol An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106) Cloranfenicol,Kloramfenikol,Levomycetin,Amphenicol,Amphenicols,Chlornitromycin,Chlorocid,Chloromycetin,Detreomycin,Ophthochlor,Syntomycin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D042967 Electron Transport Complex I A flavoprotein and iron sulfur-containing oxidoreductase complex that catalyzes the conversion of UBIQUINONE to ubiquinol. In MITOCHONDRIA the complex also couples its reaction to the transport of PROTONS across the internal mitochondrial membrane. The NADH DEHYDROGENASE component of the complex can be isolated and is listed as EC 1.6.99.3. NADH Dehydrogenase (Ubiquinone),Complex I Dehydrogenase,NADH DH I,NADH Dehydrogenase Complex 1,NADH Dehydrogenase I,NADH Q1 Oxidoreductase,NADH-CoQ Reductase,NADH-Coenzyme Q Reductase,NADH-Ubiquinone Oxidoreductase,NADH-Ubiquinone Reductase,Respiratory Complex I,Rotenone-Sensitive Mitochondrial NADH-Ubiquinone Oxidoreductase,Ubiquinone Reductase,Dehydrogenase, Complex I,NADH CoQ Reductase,NADH Coenzyme Q Reductase,NADH Ubiquinone Oxidoreductase,NADH Ubiquinone Reductase,Oxidoreductase, NADH Q1,Oxidoreductase, NADH-Ubiquinone,Reductase, NADH-Ubiquinone,Rotenone Sensitive Mitochondrial NADH Ubiquinone Oxidoreductase
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D046912 Multiprotein Complexes Macromolecular complexes formed from the association of defined protein subunits. Macromolecular Protein Complexes,Complexes, Macromolecular Protein,Complexes, Multiprotein,Protein Complexes, Macromolecular
D020543 Proteome The protein complement of an organism coded for by its genome. Proteomes
D021122 Protein Subunits Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly. Protomers,Protein Subunit,Protomer,Subunit, Protein,Subunits, Protein

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