Vice speaker of the Research Department of Neuroscience
Molecular Cell Biology
Institute of Biochemistry and Pathobiochemistry
Faculty of Medicine
Ruhr University Bochum
Universitätsstr. 150
44801 Bochum
Room:
MA 2/143
Phone:
+49 (0)234 32-28428
Email:
konstanze.winklhofer@ruhr-uni-bochum.de
The Winklhofer lab focuses on mechanisms underlying neurodegenerative diseases on the molecular, cellular and systems level. A major topic is the role of the ubiquitin system in maintaining neuronal proteostasis and integrity. Another focus are mitochondria as key organelles in orchestrating stress response and adaptive pathways as well as interorganellar communication at the interface of neuroprotective and innate immune signaling.
To address these research interests experimentally, we are using state-of-the-art techniques in cell biology, molecular biology, protein biochemistry, and advanced light microscopy, including super-resolution microscopy and live cell imaging.
Furthmann, N., Angersbach, L., Bader, V., Blusch, A., Goel, S., Sánchez-Vicente, A., Krause, L. J., Grover, P., Trinkaus, V. A., van Well, E. M., Jaugstetter, M., Tschulik, K., Damgaard, R. B., Saft, C., Ellrichmann, G., Gold, R., Koch, A., Englert, B., Glatzel, M., . . . Winklhofer, K. F. (2023). NEMO reshapes the protein aggregate interface and promotes aggrephagy by co-condensation with p62. https://doi.org/10.1101/2023.06.05.543428
Wu, Z., Berlemann, L. A., Bader, V., Sehr, D. A., Dawin, E., Covallero, A., Meschede, J., Angersbach, L., Showkat, C., Michaelis, J. B., Münch, C., Rieger, B., Namgaladze, D., Herrera, M. G., Fiesel, F. C., Springer, W., Mendes, M., Stepien, J., Barkovits, K., . . . Winklhofer, K. F. (2022). Lubac assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus. The EMBO Journal, 41(24), e112006. https://doi.org/10.15252/embj.2022112006
Schlagowski, A. M., Knöringer, K., Morlot, S., Sánchez Vicente, A., Flohr, T., Krämer, L., Boos, F., Khalid, N., Ahmed, S., Schramm, J., Murschall, L. M., Haberkant, P., Stein, F., Riemer, J., Westermann, B., Braun, R. J., Winklhofer, K. F., Charvin, G., & Herrmann, J. M. (2021). Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol. The EMBO Journal, 40(16), e107913. https://doi.org/10.15252/embj.2021107913
Duscha, A., Gisevius, B., Hirschberg, S., Yissachar, N., Stangl, G. I., Dawin, E., Bader, V., Haase, S., Kaisler, J., David, C., Schneider, R., Troisi, R., Zent, D., Hegelmaier, T., Dokalis, N., Gerstein, S., Del Mare-Roumani, S., Amidror, S., Staszewski, O., . . . Winklhofer, K. F., Haghikia, A. (2020). Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism. Cell, 180(6), 1067-1080.e16. https://doi.org/10.1016/j.cell.2020.02.035
Meschede, J., Šadić, M., Furthmann, N., Miedema, T., Sehr, D. A., Müller-Rischart, A. K, Bader, V., Berlemann, L. A., Pilsl, A., Schlierf, A, Barkovits, K., Kachholz, B., Rittinger, K., Ikeda, F., Marcus, K., Schaefer, L., Tatzelt, J, & Winklhofer, K. F. (2020). The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC. Science Signaling, 13(617). https://doi.org/10.1126/scisignal.aav1256
van Well, E. M., Bader, V., Patra, M., Sánchez-Vicente, A., Meschede, J., Furthmann, N., Schnack, C., Blusch, A., Longworth, J., Petrasch-Parwez, E., Mori, K., Arzberger, T., Trümbach, D, Angersbach, L., Showkat, C., Sehr, D. A., Berlemann, L. A., Goldmann, P., Clement, A. M., . . . Winklhofer, K. F. (2019). A protein quality control pathway regulated by linear ubiquitination. The EMBO Journal, 38(9). https://doi.org/10.15252/embj.2018100730
Woerner, A. C., Frottin, F., Hornburg, D., Feng, L. R., Meissner, F., Patra, M., Tatzelt, J, Mann, M., Winklhofer, K. F., Hartl, F. U., & Hipp, M. S. (2016). Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science (New York, N.Y.), 351(6269), 173–176. https://doi.org/10.1126/science.aad2033
Müller-Rischart, A. K, Pilsl, A., Beaudette, P., Patra, M., Hadian, K., Funke, M., Peis, R., Deinlein, A, Schweimer, C., Kuhn, P.‑H., Lichtenthaler, S. F., Motori, E., Hrelia, S., Wurst, W, Trümbach, D, Langer, T., Krappmann, D., Dittmar, G., Tatzelt, J, & Winklhofer, K. F. (2013). The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Molecular Cell, 49(5), 908–921. https://doi.org/10.1016/j.molcel.2013.01.036
Rolland, S. G., Motori, E., Memar, N., Hench, J., Frank, S., Winklhofer, K. F., & Conradt, B. (2013). Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion. Proceedings of the National Academy of Sciences of the United States of America, 110(32), E2967-76. https://doi.org/10.1073/pnas.1303872110
Bouman, L., Schlierf, A, Lutz, A. K., Shan, J., Deinlein, A, Kast, J., Galehdar, Z., Palmisano, V., Patenge, N., Berg, D., Gasser, T., Augustin, R., Trümbach, D, Irrcher, I., Park, D. S., Wurst, W, Kilberg, M. S., Tatzelt, J, & Winklhofer, K. F. (2011). Parkin is transcriptionally regulated by ATF4: Evidence for an interconnection between mitochondrial stress and ER stress. Cell Death and Differentiation, 18(5), 769–782. https://doi.org/10.1038/cdd.2010.142