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When the cell digests itself

How ER remodeling works and inherited neurodegenerative diseases develop:

International research teams from Goethe University Frankfurt and Jena University Hospital find mechanisms involved in regulation of structure and function of endoplasmic reticulum and elucidate a development of hereditary neurodegenerative diseases.

Our cells contain a system of membrane tubes and pockets called the endoplasmic reticulum (ER) that is crucial for the production of biomolecules and is continuously built up and degraded. Degradation, known as ER phagy, is promoted by the protein ubiquitin, which controls many processes in the cell. If the proteins involved in ER phagy are defective, neurodegenerative diseases result. This has been discovered by an international research team led by Prof. Ivan Đikić, director of Institute for Biochemistry 2 and Professor at Goethe University Frankfurt and Prof. Christian Hübner from Jena University Hospital, published in two papers in the journal Nature.

These studies led to better understanding how cells control their functions and thus create something we call cellular homeostasis. In biology, this knowledge allows fascinating insights into the incredible achievements of our cells, and for medicine it is essential for understanding diseases, diagnosing it on time and helping patients with developing new therapeutic approaches.

DNA-PAINT super-resolution image of FAM134B in a Torin 1-treated U2OS cell

Publications: 1) Alexis González, Adriana Covarrubias-Pinto, Ramachandra M. Bhaskara, Marius Glogger, Santosh K. Kuncha, Audrey Xavier, Eric Seemann, Mohit Misra, Marina E. Hoffmann, Bastian Bräuning, Ashwin Balakrishnan, Britta Qualmann, Volker Dötsch, Brenda A. Schulman, Michael M. Kessels, Christian A. Hübner, Mike Heilemann, Gerhard Hummer, Ivan Dikic: Ubiquitination regulates ER-phagy and remodeling of endoplasmic reticulum. Nature (2023) 2) Hector Foronda, Yangxue Fu, Adriana Covarrubias-Pinto, Hartmut T. Bocker, Alexis González, Eric Seemann, Patricia Franzka, Andrea Bock, Ramachandra M. Bhaskara, Lutz Liebmann, Marina E. Hoffmann, Istvan Katona, Nicole Koch, Joachim Weis, Ingo Kurth, Joseph G. Gleeson, Fulvio Reggiori, Gerhard Hummer, Michael M. Kessels, Britta Qualmann, Muriel Mari, Ivan Dikić, Christian A. Hübner: Heteromeric 1 clusters of ubiquitinated ER-shaping proteins drive ER-phagy. Nature (2023)

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