Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I

Nuber, Franziska; Schimpf, Johannes; di Rago, Jean-Paul; Tribouillard-Tanvier, Déborah; Procaccio, Vincent; Martin-Negrier, Marie-Laure; Trimouille, Aurélien; Biner, Olivier; von Ballmoos, Christoph; Friedrich, Thorsten (2021). Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I. Scientific reports, 11(1), p. 12641. Springer Nature 10.1038/s41598-021-91631-3

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NADH:ubiquinone oxidoreductase (respiratory complex I) plays a major role in energy metabolism by coupling electron transfer from NADH to quinone with proton translocation across the membrane. Complex I deficiencies were found to be the most common source of human mitochondrial dysfunction that manifest in a wide variety of neurodegenerative diseases. Seven subunits of human complex I are encoded by mitochondrial DNA (mtDNA) that carry an unexpectedly large number of mutations discovered in mitochondria from patients' tissues. However, whether or how these genetic aberrations affect complex I at a molecular level is unknown. Here, we used Escherichia coli as a model system to biochemically characterize two mutations that were found in mtDNA of patients. The V253AMT-ND5 mutation completely disturbed the assembly of complex I, while the mutation D199GMT-ND1 led to the assembly of a stable complex capable to catalyze redox-driven proton translocation. However, the latter mutation perturbs quinone reduction leading to a diminished activity. D199MT-ND1 is part of a cluster of charged amino acid residues that are suggested to be important for efficient coupling of quinone reduction and proton translocation. A mechanism considering the role of D199MT-ND1 for energy conservation in complex I is discussed.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Biner, Olivier Felix, von Ballmoos, Christoph


500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry




Springer Nature




Christina Schüpbach

Date Deposited:

01 Feb 2022 14:30

Last Modified:

05 Dec 2022 16:03

Publisher DOI:


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