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A03 | Role of mitofusin ubiquitylation in mitochondrial quality control

Mafalda Escobar-Henriques
CECAD Research Center/Institute for Genetics
University of Cologne

Phone: +49 - 221 / 478 84257         
E-mail: MafaldaEscobar@uni-koeln.de
For more information and contact please visit the ESCOBAR LAB.


Running time within the CRC 1218: 07/2016 - 06/2024.

Abstract

Mitochondrial shape adapts to the cellular conditions, thanks to their capacity to undergo fusion and fission events. This dynamism is important to overcome stress, for example by assisting the elimination of the damaged organelles by mitophagy. Fusion components, called mitofusins, are hubs for stress signal integration and transformation into mitochondrial morphology and mitophagy regulation. The activity of mitofusins is regulated by ubiquitylation both in yeast and mammals. In this project, we want to unravel the molecular mechanisms governing mitofusins ubiquitylation and its implications in health and disease.

Project-relevant publications

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