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Structure, function and dynamics of mitochondrial complexes

Ulrich Brandt
Radboud University Medical Center, Nijmegen,
The Netherlands

Phone: +31 24 36 67098       
E-mail: Ulrich.BrandtSpamProtectionradboudumc.nl
For more information and contact please visit the BRANDT LAB.

A hallmark of mitochondria at the molecular level is their richness in large and often membrane integral multiprotein complexes that perform a wide range of biological functions. We study the structure, mechanisms and composition of these assemblies, with a focus on the enzyme complexes of the respiratory chain. We have solved the X-ray structure of mitochondrial complex I and now aim at elucidating the molecular mechanism by which this huge membrane protein assembly of about 1,000 kDa and  more than 40 different subunits employs redox energy to pump protons across the inner mitochondrial membrane.

In recent years, we have developed complexome profiling combining blue-native electrophoresis and mass spectrometry to acquire a comprehensive inventory of the multiprotein complexes in a biological sample with a single experiment and determine their composition, molecular mass and relative abundance at the same time. For example, complexome profiling allowed us to decipher the detailed assembly pathway of human complex I. We now use this approach to study the dynamics of the mitochondrial complexome as a whole, in order to explore how the remodeling of the inventory of multiprotein complexes and their interactions contribute to functional adaptations of the organelle in response to metabolic challenges or in human disease.

Latest publications
Brandt, U. (2019). Adaptations of an ancient modular machine - Mechanism of energy conversion is conserved in the complex I superfamily. Science 363, 230-231.

Cabrera-Orefice, A., Yoga, E. G., Wirth, C., Siegmund, K., Zwicker, K., Guerrero-Castillo, S., Zickermann, V., Hunte, C., and Brandt, U. (2018). Locking loop movement in the ubiquinone pocket of complex I disengages the proton pumps. Nat. Commun. 9, 4500.

Guerrero-Castillo, S., Baertling, F., Kownatzki, D., Wessels, H.J., Arnold, S., Brandt, U., and Nijtmans, L. (2017). The assembly pathway of mitochondrial respiratory chain complex I. Cell Metabolism 25, 128-139.

Zickermann, V., Wirth, C., Nasiri, H., Siegmund, K., Schwalbe, H., Hunte, C., and Brandt, U. (2015). Mechanistic insight from the crystal structure of mitochondrial complex I. Science, 347:44-49.