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SFB 1218 Mitochondrial regulation of cellular function

A10 | Plasticity of the mitochondrial contact site and cristae organizing complex

Ulrich Brandt
International Faculty Professor, University of Cologne
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.


Completed project - runnning time within the CRC 1218: 07/2020 - 06/2024.

Abstract

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.


Project-related publications

Hevler, J. F., Albanese, P., Cabrera-Orefice, A., Potter, A., Jankevics, A., Misic, J., Scheltema, R.A., Brandt, U., Arnold, S.,  and Heck, A.J.R. (2023) MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex. Open Bio. 2023 Mar;13(3):220363. doi: 10.1098/rsob.220363. Epub 2023 Mar 1.

Patron, M., Tarasenko, D., Nolte, H., Ghosh, M.,  Ohba, Y., Lasarzewski, Y., Ahmadi, Z.A., Cabrera-Orefice, A., Eyiama, A., Kellermann, T., Rugarli, E.I., Brandt, U., Meinecke, M., Langer, T. (2022). Regulation of mitochondrial proteostasis by the proton gradient. The EMBO Journal (2022)e110476. https://doi.org/10.15252/embj.2021110476

Salscheider, S.L., Gerlich, S., Cabrera-Orefice, A., Peker, E., Rothemann, R.A., Murschall, L.M., Finger, Y., Szczepanowska, K., Ahmadi, Z. A., Guerrero-Castillo, S. Erdogan, A., Becker, M. Ali, M., Habich, M., Petrungaro, C., Burdina, N., Schwarz, G., Klußmann, M., Neundorf, I., Stroud, D.A., Ryan, M.T., Trifunovic, A., Brandt, U., and Riemer, J. (2022). AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5. EMBO Journal, 41, e110784.

Patron, M., Tarasenko, D., Nolte, H., Kroczek, L., Ghosh, M., Ohba, Y., Lasarzewski, Y., Ahmadi, Z.A., Cabrera-Orefice, A., Eyiama, A., Kellermann, T., Rugarli, E., Brandt, U., Meinecke, M., Langer, T. (2022) Regulation of mitochondrial proteostasis by the proton gradient. EMBO Journal, 41, e110476.

Guerrero-Castillo, S., van Strien J., Brandt, U. and Arnold, S. (2021) Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome. EMBO Journal, 40, e108648.

Hevler J.F., Chiozzi, R.Z., Cabrera-Orefice, A., Brandt U., Arnold, S, and Albert J. R. Heck, A.J.R. (2021) Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain. Proc. Natl. Acad. Sci. USA, 118, e2106950118.

Szczepanowska, K., Senft, K., Heidler, J., Herholz, M., Kukat, M.A., Höhne, N., Hofsetz, E., Becker, C.,  Kaspar, S., Giese, H., Zwicker, K., Guerrero-Castillo, S, Baumann, L., Kauppila, J., Rumyantseva, A., Müller, S., Frese, C.K., Brandt, U., Riemer, J., Wittig, I., and Trifunovic, A. (2020) A salvage pathway maintains highly functional respiratory complex I. Nature Communications 11, 1643.

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.