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B03 | Ubiquitin-dependent coordination of mitochondrial-cytoplasmic quality control

Thorsten Hoppe
CECAD Research Center/Institute for Genetics
University of Cologne

E-mail: Thorsten.HoppeSpamProtectionuni-koeln.de
Phone: +49 - 221 / 478 84218
For more information and contact please visit the HOPPE LAB.


Running time within the CRC 1218: 07/2016 - 06/2028.
 

Abstract

Ubiquitin-dependent degradation of outer mitochondrial membrane (OMM) proteins has been implicated in the dynamic regulation of mitochondrial-cytosolic communication, but little is known about its mechanistic regulation and physiological consequences. To monitor OMM protein turnover in a multicellular organism, we developed a fluorescent reporter assay in C. elegans based on an OMM-anchored GFP-tagged reporter substrate. The main goal of the proposed research is to understand how physiological and metabolic changes regulate ubiquitin-dependent OMM protein degradation in an organismal context.
 

Project-related publications

Müller L, Salman S, Hoppe T (2024). Chemical cross-linking to study protein self-assembly in cellulo. STAR Protoc, 2024 vol. 5(2) p. 103032. DOI: doi: 10.1016/j.xpro.2024.103032.

Li Q. and Hoppe T (2023). Role of amino acid metabolism in mitochondrial homeostasis. Front Cell Dev Biol. 10.3389/fcell.2023.1127618

Hermeling, J. CW., Herholz, M., Baumann, L., Cores, E.C., Zečić, A., Hoppe, T., Riemer, J., Trifunovic, A. (2022). Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans. Redox Biology 2022,  https://doi.org/10.1016/j.redox.2022.102533

Ravanelli, S., Li, Q., Annibal, A., Trifunovic, A., Antebi, A., Hoppe, T. (2022). Reprograming of proteasomal degradation by branched chain amino acid metabolism.  Aging Cell 2022, https://doi.org/10.1111/acel.13725

Balaji, V., Müller, L., Lorenz, R., Kevei, E., Zhang, W.H., Santiago, U., Gebauer, J., Llamas, E., Vilchez, D., Camacho, C.J., Pokrzywa, W., Hoppe T. (2022). A Dimer-Monomer Switch Controls CHIP-Dependent Substrate Ubiquitylation and Processing. Mol Cell. 2022, doi: https://doi.org/10.1016/j.molcel.2022.08.003

Müller, L., Kutzner, C.E., Balaji, V., Hoppe, T. (2021). In vitro analysis of E3 ubiquitin ligase function. J Vis Exp. 171, doi: 10.3791/62393.

Albert, M.C., Brinkmann, K., Pokrzywa, W., Günther, S.D., Krönke, M., Hoppe, T*., Kashkar, H*. (2020). CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage. Cell Death Dis. 11:740 *Corresponding author

Hoppe, T., Cohen, E. (2020). Organismal Protein Homeostasis Mechanisms. doi: 10.1534/genetics.120.301283

Ravanelli, S., den Brave, F., Hoppe, T. (2020). Mitochondrial Quality Control Governed by Ubiquitin. Front. Cell Dev. Biol. | doi: 10.3389/fcell.2020.00270

Balaji, V. and Hoppe, T. (2020). Regulation of E3 ubiquitin ligases by homotypic and heterotypic assembly.  F1000 Research 2020, 9 (F1000 Faculty Rev), 88.

Tawo, R., Pokrzywa, W., Kevei, E., Akyuz, M.E., Balaji, V., Arian, S., Höhfeld, J., and Hoppe, T. (2017). The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover. Cell 169, 470-482.

Franz, A., Ackermann, L. and Hoppe, T.  (2016). Ring of change: CDC48/p97 drives protein dynamics at chromatin. Front. Genet. 7, 73.

Franz, A., Kevei, É., and Hoppe, T. (2015). Double-edged alliance: mitochondrial surveillance by the UPS and autophagy. Curr. Opin. Cell Biol. 4, 37:18-27.

Segref, A., Kevei, É., Pokrzywa, W., Schmeisser, K., Mansfeld, J., Livnat-Levanon, N., Ensenauer, R., Glickman, M.H., Ristow, M., and Hoppe, T. (2014). Pathogenesis of human mitochondrial diseases is modulated by reduced activity of the ubiquitin/proteasome system. Cell Metab.  19, 642-652.

Livnat-Levanon, N., Kevei, É., Kleifeld, O., Krutauz, D., Segref, A., Rinaldi, T., Erpapazoglou, Z., Cohen, M., Reis, N., Hoppe, T., Glickman M.H. (2014). Reversible 26S Proteasome disassembly upon mitochondrial stress. Cell Rep.  7, 1371-1380.

Brinkmann, K., Zigrino, P., Witt, A., Schell, M., Ackermann, L., Broxtermann, P., Schüll, S., Andree, M., Coutelle, O., Yazdanpanah, B., Seeger, J.M., Klubertz, D., Drebber, U., Hacker, U.T., Krönke, M., Mauch, C., Hoppe, T., Kashkar, H. (2013). Ubiquitin C-terminal hydrolase-L1 potentiates cancer chemosensitivity by stabilizing NOXA. Cell Rep. 3, 881-891.

Segref, A., Torres, S., and Hoppe, T. (2011). A Screenable in vivo Assay to Study Proteostasis Networks in Caenorhabditis elegans. Genetics 187, 1235-1240.

Janiesch, P.C., Kim, J., Mouysset, J., Barikbin, R., Lochmüller, H., Cassata, G., Krause, S., and Hoppe, T. (2007). The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to human myopathy. Nat. Cell Biol. 9, 379-390.

Springer, W., Hoppe, T., Schmidt, E., and Baumeister, R. (2005). A Caenorhabditis elegans Parkin mutant with altered solubility couples α-synuclein aggregation to proteotoxic stress. Hum. Mol. Genet. 14, 3407-3423.

Hoppe, T., Cassata, G., Barral, J.M., Springer, W., Hutagalung, A.H., Epstein, H.F., and Baumeister, R. (2004). Regulation of the Myosin-Directed Chaperone UNC-45 by a Novel E3/E4-Multiubiquitylation Complex in Caenorhabditis elegans. Cell 118, 337-349.