A03 | Cellular quality control by mitofusins and ubiquitin
Mafalda Escobar-Henriques
Institute for Genetics
Center of Molecular Biosciences, CoMB
University of Cologne
Phone: +49 - 221 / 470-89053
E-mail: MafaldaEscobar@uni-koeln.de
For more information and contact please visit the ESCOBAR LAB.
Running time within the CRC 1218: 07/2016 - 06/2028.
Abstract
Mitochondrial plasticity contributes to protein quality and neuronal integrity. Mitofusins, mitochondrial fusion factors, can sense and respond to many different stimuli through their ubiquitylation. We recently reported on a ubiquitin-dependent proteolytic stress response at the mitochondrial surface that merges these many different signals into a common cellular response. Now we wish to further explore this quality control pathway and unravel how mitofusins and ubiquitin support cellular triage of damaged mitochondrial components. Our project aims to elucidate molecular mechanisms providing protection to mitochondria under stress.
Project-relevant publications
Anton, V., Buntenbroich, I., Simões, T., Joaquim, M., Müller, L., Büttner, R., Odenthal, M., Hoppe, T., Escobar-Henriques, M. (2023). E4 ubiquitin ligase promotes mitofusin turnover and mitochondrial stress response. Molecular Cell. DOI: doi.org/10.1016/j.molcel.2023.07.021. (Open access).
Buntenbroich, I., Anton, V., Perez-Hernandez, D., Simões, T., Gaedke, F., Schauss, A., Dittmar, G., Riemer, J., Escobar-Henriques, M. (2023). Docking and stability defects in mitofusin highlight the proteasome as a potential therapeutic target. iScience. 2023 Jun 7;26(7):107014. doi: 10.1016/j.isci.2023.107014
Joaquim M., Escobar-Henriques M. (2020). Role of Mitofusins and Mitophagy in Life or Death Decisions. DOI: 10.3389/fcell.2020.572182
Escobar-Henriques M., Vincent A. (2020) Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion. DOI: 10.3390/ijms21186841
Schuster, R., Anton, V., Simoes, T., Altin, S., den Brave, F., Hermanns, T., Hospenthal, M., Komander, D., Dittmar, G., Dohmen, R.J., Escobar-Henriques, M. (2019). Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation. Life Sci. Alliance, 3(1). pii: e201900476. doi: 10.26508/lsa.201900476. Print 2020 Jan.
Anton, V., Buntenbroich, I., Schuster, R., Babatz, F., Simoes, T., Altin, S., Calabrese, G., Riemer, J., Schauss, A.C., Escobar-Henriques, M. (2019). Plasticity in salt-bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition. Life Sci. Alliance, 2(6). pii: e201900491.
Escobar-Henriques, M. and Joaquim, M. (2019). Mitofusins: Disease Gatekeepers and Hubs in Mitochondrial Quality Control by E3 Ligases. Front. Physiol. 10, 517.
Escobar-Henriques, M., Altin, S., and Brave, F.D. (2019). Interplay between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis. (Book chapter), in: Sumoylation and Ubiquitylation: Current and Emerging Concepts, Caister Academic Publishing. Open access in: Curr. Issues Mol. Biol. 35, 35-58.
Schuster, R., Simoes, T., den Brave, F., and Escobar-Henriques, M. (2018). Separation and visualization of low abundant ubiquitylated forms. BIO-Protocols 8, DOI: 10.21769/BioProtoc.3081.
Simões, T., Schuster, R., den Brave, F., Escobar-Henriques, M. (2018). Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion. Elife 7. pii: e30015. doi: 10.7554/eLife.30015. [Epub ahead of print].
Escobar-Henriques, M. and Langer, T. (2014). Dynamic survey of mitochondria by ubiquitin. EMBO Rep. 15, 231-243.
Anton, F., Dittmar, G., Langer, T., and Escobar-Henriques, M. (2013). Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along independent pathways. Mol. Cell 49, 487-498.
Escobar-Henriques, M., and Anton, F. (2013). Mechanistic perspective of mitochondrial fusion: tubulation vs. fragmentation. Biochim Biophys Acta 1833, 162-175.
Escobar-Henriques, M. (2014). Mitofusins: ubiquitylation promotes fusion. Cell Res. 24, 387-388.
Anton, F., Fres, J.M., Schauss, A., Pinson, B., Praefcke, G.J., Langer, T., and Escobar-Henriques, M. (2011). Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion. J. Cell Sci. 124, 1126-1135