B06 | Targeting BCL2 protein family in mitochondrial diseases
Hamid Kashkar
Institute for Molecular Immunology, University of Cologne
CECAD Research Center
Joseph-Stelzmann-Str.26
50931 Cologne
E-mail: H.Kashkar
uni-koeln.de
Phone: +49 - 221 / 478 84091
For more information and contact please visit the KASHKAR LAB.
Running time within the CRC 1218: 07/2016 - 06/2028.
Abstract
Our previous studies using a mouse model for mitochondrial hepatopathy identified mitochondrial apoptosis as an important surveillance mechanism that counteracts the manifestation of the mitochondrial disease in liver. Here, we aim to investigate the (patho)physiological role of apoptosis in mitochondrial diseases caused by mtDNA mutation in mice. This project will explore the role of apoptosis in different tissues affected by mitochondrial dysfunction.
Project-related publications
Schorn, F., Werthenbach, J. P., Hoffmann, M., Daoud, M., Stachelscheid, J., Schiffmann, L.M., Hildebrandt, X., Lyu, S.I., Peltzer, N., Quaas, A., Vucic, D., Silke, J., Pasparakis, M., Kashkar, H. (2023). cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation. The EMBO Journal 2023 Oct 4:e113614. DOI: 10.15252/embj.2023113614
Flores-Romero, H., Hohorst, L., John, M., Albert, M-C., King, L. E, Beckmann, L., Szabo, T., Hertlein, V., Luo, X., Villunger, A., Frenzel, L. P., Kashkar, H., Garcia-Saez, A. J. (2021). BCL-2-family protein tBID can act as a BAX-like effector of apoptosis. The EMBO Journal (2021)e108690. https://doi.org/10.15252/embj.2021108690
Geueke, A., Mantellato, G., Kuester, F., Schettina, P., Nelles, M., Seeger, J.M., Kashkar, H., Niemann, C. (2021). The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function
EMBO Rep (2021)e52301. https://doi.org/10.15252/embr.202052301
He, L., Sehrawat, T.S., Verma, V.K., Navarro-Corcuera, A., Sidhu, G., Mauer, A., Luo, X., Katsumi, T., Chen, J., Shah, S., Arab, J.P., Cao, S., Kashkar, H., Gores, G.J., Malhi, H., Shah, V.H. (2021).
XIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC
Front. Physiol., 07 May 2021
Kirschberg, M., Heuser, S., Marcuzzi, G.P., Hufbauer, M., Seeger, J.M., Đukić, A., Tomaić, V., Majewski, S., Wagner, S., Wittekindt, C., Würdemann, N., Klussmann, J.P., Quaas, A., Kashkar, H., Akgül, B. (2020).
ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers.
Sci Rep. 2020 Oct 15;10(1):17339. doi: 10.1038/s41598-020-74311-6. PMID: 33060693
Albert, M.C., Brinkmann, K., Pokrzywa, W., Günther, S.D., Krönke, M., Hoppe, T*., Kashkar H*. (2020). CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage. Cell Death Dis. 11:740 *Corresponding author
Schiffmann, L.M., Werthenbach, J.P., Heintges-Kleinhofer, F., Seeger, J.M., Fritsch, M., Günther, S.D., Willenborg, S., Brodesser, S., Lucas, C., Jüngst, C., Albert, M.C., Schorn, F., Witt, A., Moraes, C.T., Bruns, C., Pasparakis, M., Krönke, M., Eming, S.A., Coutelle, O., Kashkar, H. (2020). Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat. Commun. 11:3653
Lampl, S., Janas, M.K., Donakonda, S., Brugger, M., Lohr, K., Schneider, A., Manske, K., Sperl, L.E., Wettmarshausen, J., Müller, C., Laschinger, M., Hartmann, D., Hüser, N., Perrochi, F., Schmidt-Kopplin, P., Hagn, F., Zender, L., Hornung, V., Borner, C., Pichlmair, A., Kashkar, H., Klingenspor, M., Prinz, M., Schreiner, S., Conrad, M., Jost, P.J., Zischka, H., Steiger, K., Krönke, M., Zehn, D., Protzer, U., Heikenwälder, M., Knolle, P.A., Wohlleber, D. (2020). Reduced mitochondrial resilience enables non-canonical induction of apoptosis after TNFR signaling in virus-infected hepatocytes. J. Hepatol [Epub ahead of print]
Haumann, S., Boix, J., Knuever, J., Bieling, A., Vila Sanjurjo, A., Elson, J.L., Blakely, E.L., Taylor, R.W., Riet, N., Abken, H., Kashkar, H., Hornig-Do, H.T., Wiesner, R.J. (2020). Mitochondrial DNA mutations induce mitochondrial biogenesis and increase the tumorigenic potential of Hodgkin and Reed-Sternberg cells. Carcinogenesis [Epub ahead of print]
Holzer, T., Probst, K., Etich, J., Auler, M., Georgieva, V., Bluhm, B., Frie, C., Heilig, J., Niehoff, A., Nüchel, J., Plomann, M., Seeger, J.M., Kashkar, H., Baris, O.R., Wiesner, R.J., Brachvogel, B. (2019). Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J. Cell Biol. 218(6):1853-1870
Habich, M., Salscheider, S.L., Murschall, L.M., Hoehne, M.N., Fischer, M., Schorn, F., Petrungaro, C., Ali, M., Erdogan, A.J., Abou-Eid, S., Kashkar, H., Dengjel, J., Riemer, J. (2019). Vectorial import via a metastable disulphide-linked complex allows for a quality control step and import by the mitochondrial disulphide relay Cell Rep. 26(3):759-774
Saita, S., Nolte, H., Fiedler, K.U., Kashkar, H., Venne, A.S., Zahedi, R.P., Krueger, M., Langer, M. (2017). PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis. Nat. Cell Biol. 19:318–328
Knittel, G.*, Liedgens, P.*, Korovkina, D.*, Seeger, J.M.*, Al-Baldawi, Y., Al-Maarri, M., Fritz, C., Vlantis, K., Bezhanova, S., Scheel, A.H., Wolz, O.O., Reimann, M., Möller, P., López, C., Schlesner, M., Lohneis, P., Weber, A.N., Trümper, L., Consortium, I.M., Staudt, L.M., Ortmann, M., Pasparakis, M., Siebert, R., Schmitt, C.A., Klatt, A.R., Wunderlich, F.T., Schäfer, S.C., Persigehl, T., Montesinos-Rongen, M., Odenthal, M., Büttner, R., Frenzel, L.P.§, Kashkar, H.§, Reinhardt, H.C.§. (2016). B cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B cell lymphoma in mice. Blood 127(22):2732-41. * and § equal contribution
Schüll, S., Günther, S.D., Brodesser, S., Seeger, J.M., Tosetti, B., Wiegmann, K., Pongratz, C., Diaz, F., Witt, A., Andree, M., Brinkmann, K., Krönke, M., Wiesner, R.J., Kashkar, H. (2015). Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6. Cell Death Dis. 6:e1691