Research group Biochemistry

Apoptotic cells remove themselves and thereby protect their multicellular organism from serious pathologies, such as tumor diseases. Apoptotic cells shrink and form apoptotic vesicles into which they pack their contents for complete removal by phagocytosis. Apoptosis can be induced either by signals (death receptor ligands) at the cell surface or by cell stress. In both cases, BCL-2 family proteins play central roles in signal integration and the molecular decision between regulated suicide by apoptosis and survival.

This decision takes place at the outer membrane of mitochondria. In this process, the pro-apoptotic BCL-2 BAX and the very similar BAK have a special function. Activation of both proteins leads to the initiation of a signaling cascade of caspases, proteases whose activity irreversably commits a cell to apoptosis. Therefore, activation of BAX and BAK is the molecular decision to apoptosis. Active BAX/BAK can permeabilize the outer mitochondrial membrane so that intermembrane space proteins, such as cytochrome c, are released. This release causes an interruption of mitochondrial respiration and, the formation of the apoptosome to activate caspase-9. Although the central importance of BAX/BAK activation not only for the prevention but also the therapy of tumor diseases and other severe pathologies is undisputed, this important physiological process is the center of important questions.

Our laboratory is mainly concerned with the following questions:

• How are BAX and BAK regulated in cells depending on cell stress and stress response?
• How do inhibition and activation of BAX and BAK work?
• Can we predict whether a therapy will activate BAX and BAK in target cells?
• Are there ways to circumvent the cell-intrinsic regulation of BAX and BAK?
• How do BAX and BAK activate caspases?

2022

• Wolf, P.; Schöniger, A.; Edlich, F. Pro-apoptotic complexes of BAX and BAK on the outer mitochondrial membrane. Biochimica et biophysica acta. 2022. 1869 (10). 
  DOI: 10.1016/j.bbamcr.2022.119317
• Kontchou, C. W.; Gentle, I. E.; Weber, A.; Schöniger, A.; Edlich, F.; Haecker, G. Chlamydia trachomatis inhibits apoptosis in infected cells by targeting the pro-apoptotic proteins Bax and Bak. Cell death and differentiation. 2022. S. 2046–2059.
  DOI: 10.1038/s41418-022-00995-0
• Schöniger, A.; Wolf, P.; Edlich, F. How Do Hexokinases Inhibit Receptor-Mediated Apoptosis? Biology. 2022. 11 (3).
  DOI: 10.3390/biology11030412

2021

• Lauterwasser, J.; Fimm-Todt, F.; Oelgeklaus, A.; Schreiner, A.; Funk, K.; Falquez, H.; Klesse, R.; Jahreis, G.; Zerbes, R. M.; O'Neil, K.; van der Laan, M.; Luo, X.; Edlich, F. Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria. Proceedings of the National Academy of Sciences of the United States of America. 2021. 118 (33).
  DOI: 10.1073/pnas.2021175118
• Darweesh, O.; Al-Shehri, E.; Falquez, H.; Lauterwasser, J.; Edlich, F.; Patel, R. Identification of a novel Bax-Cdk1 signalling complex that links activation of the mitotic checkpoint to apoptosis. Journal of cell science. 2021. 134 (8). 
  DOI: 10.1242/jcs.244152

2020

• Jayavelu, A.K.; Schnöder, T.M.; Perner, F.; Herzog, C.; Meiler, A.; Krishnamoorthy, G.; Huber, N.; Mohr, J.; Edelmann-Stephan, B.; Austin, R.; Brandt, S.; Palandri, F.; Schröder, N.; Isermann, B.; Edlich, F.; Sinha, A.U.; Ungelenk, M.; Hübner, C.A.; Zeiser, R.; Rahmig, S.; Waskow, C.; Coldham, I.; Ernst, T.; Hochhaus, A.; Jilg, S.; Jost, P.J.; Mullally, A.; Bullinger, L.; Mertens, P.R.; Lane, S.W.; Mann, M.; Heidel, F.H. Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms. Nature. 2020. 588 (7836). 
  DOI: 10.1038/s41586-020-2968-3
• Funk, K.; Czauderna, C.; Klesse, R.; Becker, D.; Hajduk, J.; Oelgeklaus, A.; Reichenbach, F.; Fimm-Todt, F.; Lauterwasser, J.; Galle, P.R.; Marquardt, J.U.; Edlich F. BAX redistribution induces apoptosis resistance and selective stress sensitivity in human HCC. Cancers. 2020. 12 (6). 
  DOI: 10.3390/cancers12061437

2017

• Cakir, Z.; Funk, K.; Lauterwasser, J.; Todt, F.; Zerbes, R.M.; Oelgeklaus, A.; Tanaka, A.; van der Laan, M.; Edlich, F. Parkin promotes proteasomal degradation of misregulated BAX. Journal of Cell Science. 2017. 130 (17)
  DOI: 10.1242/jcs.200162
• Reichenbach, F.; Wiedenmann, C.; Schalk, E.; Becker, D.; Funk, K.; Scholz-Kreisel, P.; Todt, F.; Wolleschak, D.; Döhner, K.; Marquardt, J.U.; Heidel, F.; Edlich, F. Mitochondrial BAX determines the predisposition to apoptosis in human AML. Clinical Cancer Research. 2017. 23 (16)
  DOI: 10.1158/1078-0432.CCR-16-1941
• Andreu-Fernández, V.; Sancho, M.; Genovés, A.; Lucendo, E.; Todt, F.; Lauterwasser, J.; Funk, K.; Jahreis, G.; Pérez-Payá, E.; Mingarro, I.; Edlich, F.; Orzáez, M. Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes. Proceedings of the National Academy of Sciences of the United States of America. 2017. 114 (2).
  DOI: 10.1073/pnas.1612322114

2015

• Todt, F.; Cakir, Z.; Reichenbach, F.; Emschermann, F.; Lauterwasser, J.; Kaiser, A.; Ichim, G.; Tait, S.W.G.; Frank, S.; Langer, H.F.; Edlich, F. Differential retrotranslocation of mitochondrial Bax and Bak. The EMBO Journal. 2015. 34.
  DOI: 10.15252/embj.201488806

2013

• Todt, F.; Cakir, Z.; Reichenbach, F.; Youle, R.J.; Edlich, F. The C-terminal helix of Bcl-x(L) mediates Bax retrotranslocation from the mitochondria. Cell Death & Differentiation. 2013. 20.
  DOI: 10.1038/cdd.2012.131

2011

• Edlich, F.; Banerjee, S.; Suzuki, M.; Cleland, M.M.; Arnoult, D.; Wang, C.; Neutzner, A.; Tjandra, N.; Youle, R.J. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell. 2011. 145.
  DOI: 10.1016/j.cell.2011.02.034
• Hoppins, S.; Edlich, F.; Cleland, M.M.; Banerjee, S.; McCaffery, J.M.; Youle, R.J.; Nunnari, J. The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes. Molecular Cell. 2011. 
  DOI: 10.1016/j.molcel.2010.11.030