UNIVERSITÄT ZU KÖLN

Thomas Becker
Institute for Biochemistry and Molecular Biology
University of Bonn

Phone: +49 228-73-2900
E-mail: thbeckeruni-bonn.de
For more information and contact please visit the BECKER LAB

Running time within the CRC 1218: 07/2020 - 06/2028.

Abstract

The translocase of the outer mitochondrial membrane (TOM complex) imports about 1000 different proteins into mitochondria. Three different pathways remove translocation-stalled precursor proteins from the TOM channel. We will investigate the molecular cooperation between these pathways and define how their functions are coordinated at the TOM complex. We will determine substrate-specificity and interactions of the quality control components that govern mitochondrial protein import.
 

Project-related publications

Colina-Teneorio, L., Horten, P., Scifo, E., Horvath, S.E., Klar, R.F.U., Priesnitz, C., den Brave, F., van der Laan, M., Becker, T., Song, K. and Rampelt, H. (2026) Mitochondrial contact site and cristae organizing system promotes modular assembly of cytochrome c oxidase. Cell Rep. 45, 116727. doi.org/10.1016/j.celrep.2025.116727

Zhao, X.T., Diep, D.T.V., Perciful, L., Fausten, R.M., Hugenroth, M., Höhne, P., Leite, B., Esch, B.M., Collado, J., Keller, J., Wilmes, S., Turhan, M.A., Wälte, M., Becker, T., Kümmel, D., Schuberth, C., Fernandez-Busnadiego, R., Fröhlich, F., Wedlich-Söldner, R. and Bohnert, M. (2025) The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility. Cell Rep. 44, 116475. doi.org/10.1016/j.celrep.2025.116475

den Brave, F., Mishra, S. and Becker, T. (2025) Mitochondrial heterogeneity: subpopulations with distinct metabolic activities. Sig Transduct Target Ther. 10, 36. doi.org/10.1038/s41392-025-02130-0

Jackson, J. and Becker, T. (2025) Unclogging of the TOM complex under import stress. Biol. Chem. 406(5-7):251-262. doi.org/10.1515/hsz-2025-0110

den Brave, F., Schulte, U., Fakler, B., Pfanner, N. and Becker, T. (2024) Mitochondrial complexome and import network. Trends Cell Biol. 34(7):578-594.

Steymans, I., and Becker, T. (2024) Monitoring α-helical membrane protein insertion into the outer membrane of yeast cells. Methods Enzym. 707, 39-62. doi.org/10.1016/bs.mie.2024.07.055

Borgert L, Becker T, den Brave F (2024). Conserved quality control mechanisms of mitochondrial protein import. J. Inherit. Metab. Dis. DOI:10.1002/jimd.12756.

Busto JV, Ganesan I, Mathar H, Steiert C, Schneider EF, Straub SP, Ellenrieder L, Song J, Stiller SB, Lübbert P, Chatterjee R, Elsaesser J, Melchionda L, Schug C, den Brave F, Schulte U, Klecker T, Kraft C, Fakler B, Becker T, Wiedemann N (2024). Role of the small protein Mco6 in the mitochondrial sorting and assembly machinery. Cell Rep. 43, 113805. DOI: 10.1016/j.celrep.2024.113805.

Horten P, Song K, Garlich J, Hardt R, Colina-Tenorio L, Horvath SE, Schulte U, Fakler F, van der Laan M, Becker T, Stuart RA, Pfanner N,  Rampelt H (2024). Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria. Cell Rep. 43, 113772. DOI: 10.1016/j.celrep.2024.113772.

Bhowmik R, den Brave F, Becker T (2024). Modular assembly of mitochondrial b-barrel proteins. Chapter in transmembrane-barrel proteins: methods and protocols: Methods Mol. Biol. 2778, 201-220. DOI: 10.1007/978-1-0716-3734-0_13.

den Brave F, Pfanner N, Becker T (2024). Mitochondrial entry gate as regulatory hub. Biochim. Biophys. Acta 1871, 119529. DOI: 10.1016/j.bbamcr.2023.119529.

Guhathakurta S, Erdogdu NU, Hoffmann JJ, Grzadzielewska I, Schendzielorz A, Seyfferth J, Mårtensson CU, Corrado M, Karoutas A, Warscheid B, Pfanner N, Becker T, Akhtar A (2023). COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function.Nat Metab. DOI: 10.1038/s42255-023-00904-w.

Peker, E., Weiss, K., Song, J., Zarges, C., Gerlich, S., Boehm, V., Trifunovic, A., Langer, T., Gehring, N., Becker, T. and Riemer, J. (2023). A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis. J. Cell Biol. 222, e202210019.

Coyne, L.P., Wang, X., Song, J., de Jong, E., Schneider, K., Massa, P.T., Middleton, F.A., Becker, T. and Chen, X.J. (2023). Mitochondrial protein import clogging as a mechanism of disease. eLife 12, e84330.

Schulte, U.; den Brave, F., Haupt, A., Gupta, A., Song, J., Müller, C.S., Engelke, J., Mishra, S., Mårtensson, C., Ellenrieder, L., Priesnitz, C., Straub, S.P., Doan, K.N., Kulawiak, B., Bildl, W., Rampelt, H., Wiedemann, N., Pfanner, N., Fakler, B. and Becker, T. Mitochondrial complexome reveals quality control pathways of protein import (2023). Nature. doi.org/10.1038/s41586-022-05641-w.

Takeda, H., Busto, J.V., Lindau, C., Tsutsumi, A., Tomii, K., Imai, K., Yamamori, Y., Hirokawa, T., Motono, C., Ganesan, I., Wenz, L.S., Becker, T., Kikkawa, M., Pfanner, N., Wiedemann, N. and Endo, T. (2023). A multipoint guidance mechanism for b-barrel folding on the SAM complex. Nat. Struct. Mol. Biol. doi.org/10.1038/s41594-022-00897-2.

Song, J., Steidle, L., Steymans, I., Singh, J., Sanner, A., Böttinger, L., Winter, D. and Becker, T. (2023). The mitochondrial Hsp70 controls the assembly of the F1FO-ATP synthase. Nat. Commun. 14, 39.

Rödl, S., den Brave, F., Räschle, M., Kizmaz, B., Lenhard, S., Groh, C., Becker, H., Zimmermann, J., Morgan, B., Richling, E., Becker, T. and Herrmann, J.M. (2022). The metabolite-controlled ubiquitin conjugase Ubc8 promotes mitochondrial protein import. Life Sci. Alliance 6, e202201526.

Hoffmann, J.J. and Becker, T. (2022).Crosstalk between mitochondrial protein import and lipids. Int. J. Mol. Sci. 23, 5275.

Priesnitz, C., Böttinger, L., Zufall, N., Gebert, M., Guiard, B., van der Laan, M. and Becker, T. (2022). Coupling to Pam16 differentially controls the dual role of Pam18 in protein import and respiratory chain formation. Cell Rep. 39, 1108619.

Song, J. and Becker T. (2022). Fidelity of organellar protein targeting. Curr. Opin. Cell Biol. 75:102071.

Li, X., Straub, J., Medeiros, T.C., Den Brave, F., Peker, E., Atanassov, I., Stillger, K., Michaelis, J.B., Burbridge, E., Adrain, C., Münch, C., Riemer, J., Becker, T., Pernas, L.F. (2022). Mitochondria shed their outer membrane in response to infection-induced stress. Science  • Vol 375, Issue 6577 • DOI: 10.1126/science.abi4343

Winter, D. and Becker, T. (2021). Surveying the mitochondrial proteome. Nature Cell Biology 23, 1216-1217.

den Brave, F., Gupta, A., Becker, T. (2021). Protein Quality Control at the Mitochondrial Surface. Front. Cell Dev. Biol. DOI: https://doi.org/10.3389/fcell.2021.795685

den Brave, F., Engelke, J. and Becker, T. (2021). Quality control of protein import into mitochondria. Biochem. J. 478, 3125-3143.

Kelly, B., Carrizo, G.E., Edwards-Hicks, J., Sanin, D.E., Stanczak, M.A., Priesnitz, C., Flachsmann, L.J., Curtis, J.D., Mittler, G., Musa, Y., Becker, T., Buescher, J.M. and Pearce, E.L. (2021). Sulfur sequestration promotes multicellularity during nutrient limitation. Nature 591, 471-476.

Takeda, H., Tsutsumi, A., Nishizawa, T., Lindau C., Busto, J.V., Wenz, L.S., Ellenrieder, L., Imai, K., Straub, S.P., Mossmann, W., Qiu, J., Yamamori, Y., Tomii, K., Suzuki, J., Murata, T., Ogasawara, S., Nureki, O., Becker, T., Pfanner, N., Wiedemann, N., Kikkawa, M. and Endo, T. (2021). Mitochondrial sorting and assembly machinery operates by b-barrel switching. Nature 590, 163-169.

Song, J., Herrmann, J.M. and Becker, T. (2021).Quality control of the mitochondrial proteome. Nat. Rev. Mol. Cell Biol. 22, 54-70.

Gupta, A. and Becker, T. (2021). Mechanisms and pathways of mitochondrial outer membrane protein biogenesis. Biochim. Biophys. Acta 1862, 148323.

den Brave, F. and Becker, T. (2020). Supercomplex formation boosts respiration. EMBO Rep. e51830

Doan, K.N., Grevel, A., Mårtensson, C.U., Ellenrieder, L., Thornton, N., Wenz, L.S., Opalinski, L., Guiard, B., Pfanner, N., Becker, T. (2020). The mitochondrial import complex MIM functions as main translocase for a-helical outer membrane proteins. Cell Rep. 31, 107567.

Mårtensson, C.U., Priesnitz, C., Song, J., Ellenrieder, L., Doan, K.N., Boos, F., Floerchinger, A., Zufall, N., Oeljeklaus, S., Warscheid, B., Becker, T. (2019). Mitochondrial protein translocation-associated degradation. Nature 569, 679-683.

Ellenrieder, L., Dieterle, M.P., Doan, K.N., Mårtensson, C.U., Floerchinger, A., Campo, M.L., Pfanner, N., Becker, T. (2019). Dual role of mitochondrial porin in metabolite transport across the outer membrane and protein transfer to inner membrane. Mol. Cell 73, 1056-1057.

Araiso, Y., Tsutsumi, A., Qiu, J., Imai, K., Shiota, T., Song, J., Lindau, C., Wenz, L.S., Sakaue, H., Yunoki, K., Kawano, S., Suzuki, J., Wischnewski, M., Schütze, C., Ariyama, H., Ando, T., Becker, T., Lithgow, T., Pfanner, N., Kikkawa, M., Endo, T. (2019). Structure of mitochondrial import gate reveals distinct preprotein paths. Nature 569, 679-683.

Becker, T., Song, J, Pfanner, N. (2019). Versatility of preprotein transfer from the cytosol to mitochondria. Trends Cell Biol. 29, 679-683.

Opaliński, Ł., Song, J., Priesnitz, C., Wenz, L.S., Oeljeklaus, S., Warscheid, B., Pfanner, N., Becker, T. (2018). Recruitment of cytosolic J-proteins by TOM receptors promotes mitochondrial protein biogenesis. Cell Rep. 25, 2026-2043.

Höhr, A.I.C., Lindau, C., Wirth, C., Qiu J., Stroud, D.A., Kutik, S., Guiard, B., Hunte, C., Becker, T., Pfanner, N., Wiedemann, N. (2018). Membrane protein insertion through a mitochondrial b-barrel gate. Science 359, eaah6834.