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B06 | Role of mitochondrial outer membrane permeabilisation in mitochondrial hepatopathy

Hamid Kashkar
CECAD Research Center/Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University Hospital Cologne

E-mail: H.KashkarSpamProtectionuni-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 - 06/2024.

Abstract

Mitochondrial respiratory dysfunction in liver causes mitochondrial hepatopathy which leads to premature lethality. This project investigates the role of mitochondrial outer membrane permeabilisation (MOMP) during the course of disease pathogenesis and examines whether therapeutic interventions aiming at inducing MOMP can block disease manifestation.

Project-related publications

Albert MC, Brinkmann K, Pokrzywa W, Günther SD, 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 LM, Werthenbach JP, Heintges-Kleinhofer F, Seeger JM, Fritsch M, Günther SD, Willenborg S, Brodesser S, Lucas C, Jüngst C, Albert MC, Schorn F, Witt A, Moraes CT, Bruns C, Pasparakis M, Krönke M, Eming SA, Coutelle O, Kashkar H. (2020) Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat. Commun. 11:3653

Lampl S, Janas MK, Donakonda S, Brugger M, Lohr K, Schneider A, Manske K, Sperl LE, 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 PJ, Zischka H, Steiger K, Krönke M, Zehn D, Protzer U, Heikenwälder M, Knolle PA, 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 JL, Blakely EL, Taylor RW, Riet N, Abken H, Kashkar H, Hornig-Do HT, Wiesner RJ. (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 JM, Kashkar H, Baris OR, Wiesner RJ, Brachvogel B. (2019) Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J. Cell Biol. 218(6):1853-1870

Habich M, Salscheider SL, Murschall LM, Hoehne MN, Fischer M, Schorn F, Petrungaro C, Ali M, Erdogan AJ, 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 KU, Kashkar H, Venne AS, Zahedi RP, 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 JM*, Al-Baldawi Y, Al-Maarri M, Fritz C, Vlantis K, Bezhanova S, Scheel AH, Wolz OO, Reimann M, Möller P, López C, Schlesner M, Lohneis P, Weber AN, Trümper L, Consortium IM, Staudt LM, Ortmann M, Pasparakis M, Siebert R, Schmitt CA, Klatt AR, Wunderlich FT, Schäfer SC, Persigehl T, Montesinos-Rongen M, Odenthal M, Büttner R, Frenzel LP§Kashkar H§, Reinhardt HC§. (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 SD, Brodesser S, Seeger JM, Tosetti B, Wiegmann K, Pongratz C, Diaz F, Witt A, Andree M, Brinkmann K, Krönke M, Wiesner RJ, Kashkar H. (2015) Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6. Cell Death Dis. 6:e1691