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B05 - Role of mitochondria in the regulation of intestinal epithelial cell death and inflammation

Manolis Pasparakis
CECAD Research Center/Institute for Genetics
University of Cologne

E-mail: pasparakisSpamProtectionuni-koeln.de
Phone: +49 - 221 / 478 84349
For more information and contact please visit the PASPARAKIS LAB.

Abstract

The project aims to study the role of mitochondria in the regulation of intestinal homeostasis and inflammation using genetic mouse models. Specifically, the possible in vivo role of mitochondrial fission in facilitating epithelial cell death (apoptotic, necroptotic) in response to immunological, microbial or chemical challenges will be addressed. In addition, we will address in vivo how mitochondrial oxidative phosphorylation defects affect epithelial cell function and intestinal homeostasis.

Project-related publications

Grab, J., Suarez, I., van Gumpel, E., Winter, S., Schreiber, F., Esser, A., Holscher, C., Fritsch, M., Herb, M., Schramm, M., Wachsmuth, L., Pallasch, C., Pasparakis, M., Kashkar, H., and Rybniker, J. (2019). Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition. Nat. Commun. 10, 688.

Vlantis, K., Wullaert, A., Polykratis, A., Kondylis, V., Dannappel, M., Schwarzer, R., Welz, P., Corona, T., Walczak, H., Weih, F., Klein, U., Kelliher, M., and Pasparakis, M. (2016). NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-kappaB-Dependent and -Independent Functions. Immunity 44, 553-567.

Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A.., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., Zelic, M., Kirsch, P., Basic, M., Bleich, A., Kelliher, M., Pasparakis. M. (2014). RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 513, 90-94.

Welz, P.S., Wullaert, A., Vlantis, K., Kondylis, V., Fernandez-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., and Pasparakis, M. (2011). FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477, 330-334.

Nenci, A., Becker, C., Wullaert, A., Gareus, R., van Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C., Madison, B.,… Pasparakis, M. (2007). Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557-561.