A10 | Plasticity of the mitochondrial contact site and cristae organizing complex
International Faculty Professor, University of Cologne
Radboud University Medical Center, Nijmegen,
Running time within the CRC 1218: 07/2020 - 06/2024.
Mitochondrial morphology varies markedly among different tissues, but the functional ramifications of this structural plasticity remain unclear. Cristae, invaginations of the inner mitochondrial membrane, are among the most flexible structures and the mitochondrial contact site and cristae organizing (MICOS) complex acts as a key player in controlling their shape. We will study the precise composition and structure of the MICOS complex in different tissues and the functional consequence of its plasticity, to shed light on the mechanisms linking cristae structure to physiological adaptations of mitochondria.
Van Strien, J., Sergio Guerrero-Castillo, S., Chatzispyrou, I.A., Houtkooper, R.H., Brandt, U., Huynen, M.A. (2019). COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome. Bioinformatics 17, 3083-3091.
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.
Huynen, M.A., Mühlmeister, M., Gotthardt, K., Guerrero-Castillo, S. and Brandt, U. (2016). Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex. Biochim, Biophys. Acta – Mol. Cell Res. 1863, 91-101.
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.