Protein-membrane interactions in programmed cell death

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Protein-membrane interactions play a pivotal role in the regulation of programmed cell death (apoptosis), with Bcl-2 proteins serving as key mediators of this process. These proteins, which include both pro-apoptotic and anti-apoptotic members, directly interact with the mitochondrial outer membrane, where they govern the release of apoptotic factors. Pro-apoptotic Bcl-2 proteins, such as Bax and Bak, promote membrane permeabilization, leading to the release of cytochrome c and subsequent activation of the caspase cascade that drives cell death. In contrast, anti-apoptotic Bcl-2 proteins, like Bcl-2 and Bcl-xL, bind to and inhibit these pro-apoptotic proteins, stabilizing the membrane and preventing apoptosis. This delicate balance between pro- and anti-apoptotic signals is tightly regulated by their interactions with membranes. Dysregulation of these processes, particularly in oxidative stress environments, is linked to diseases such as cancer and neurodegeneration. In our lab, we design and use new correlative approaches based on a combination of fluorescence microscopy and synthetic biology to understand the involvement of pro and anti-apoptotic proteins in pore formation under oxidative stress conditions.

 

 

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Selected publications:

  • Paweł Mystek, Vandana Singh, Matěj Horváth, Karolína Honzejková, Petra Riegerová, Huseyn Evci, Martin Hof, Tomáš Obšil and Radek Šachl The Minimal Membrane Requirements for BAX-induced Pore Opening upon Exposure to Oxidative Stress, Biophysical Journal, 2024. https://doi.org/10.1016/j.bpj.2024.08.017
  • Naumova, N., Šachl, R. Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins. Membranes.2020, 10 (299), 1–32
  • Dingeldein, A. P. G., Pokorná, Š., Lidman, M., Sparrman, T., Šachl, R., Hof, M., & Gröbner, G. Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization. Biophysical Journal, 112(10), 2147–2158 (2017)
  • Lidman, M, Pokorná, Š, Dingeldein, A, Sparrman ,T, Wallgren, M, Šachl, R, Hof, M and Gröbner, G The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax BBA-Biomembranes1858 1288–97 (2016)