zum Inhalt springen

A03 - Ubiquitin-dependent regulation of mitochondrial fusion

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.


Mitochondrial fusion is essential to maintain mitochondrial plasticity and cellular respiration. It depends on conserved dynamin-related proteins in the outer membrane, termed Fzo1 in yeast and Mfn1/2 in mammals, whose loss triggers neurodegeneration in disease. The activity of mitofusins is regulated by ubiquitylation both in yeast and mammals. We have identified two Fzo1 ubiquitylation pathways that either promote or inhibit fusion, thus providing a maximum response capacity to cellular needs and prevent disease. In this project, we want to unravel the molecular mechanisms governing Fzo1 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