Tübingen researchers have studied the formation of membrane pores that are critical to start the apoptosis program
When cells age or suffer damage, they are able to actively bring about their own pre-programmed death – a “suicide” process known as apoptosis. A desensitization of this process determines the change from a normal cell into a cancer cell. On the other hand, an over-functioning of apoptosis is associated to the onset of neurodegenerative diseases.
Therefore a better understanding of the underlying mechanisms is extremely important. The protein Bax is known as a key regulator of apoptosis. Researchers headed by Professor Ana García-Sáez of the University of Tübingen and Professor Joachim Spatz of the Max Planck Institute for Intelligent Systems in Stuttgart have investigated the role of Bax proteins, finding more detailed information as to how they work. The findings are published in the latest "Nature Communications".
The key step in apoptosis is the release of the protein cytochrome c and other apoptotic factors from the mitochondria into the cell interior. After this step, apoptosis induction is irreversible and cell’s fate is sealed. In order to allow this process, the mitochondrial membrane must be permeable. The research team has examined how the mitochondrial membrane becomes permeable.
Their experiments on artificial membrane systems showed that the Bax protein initially is inserted into the membrane as a single molecule. Once inserted, these monomers join up in the shortest time with a second molecule of Bax to form a stable complex, the so-called Bax dimers. From these dimers larger complexes are formed.
“Surprisingly, Bax complexes have no standard size, but we observed a mixture of different-sized Bax species”, says Dr. Katia Cosentino, a member of Professor García-Sáez team, “and these species are mostly based on dimer units”. These Bax complexes form the pores through which the cytochrome c exits the mitochondrial membrane.
The process of pore formation is finely controlled by other proteins. Some enable the assembly of Bax-elements, while others induce their dismantling. “The differing size of the Bax complexes in the pore formation is likely part of the reason why earlier investigations on pore formation conveyed in contradictory results” says Katia Cosentino.
The researchers can now make some initial recommendations for medical intervention in the apoptotic process: In order to promote this cell “suicide,” it should be enough to initiate the first step of activating Bax proteins – because the subsequent steps of self-organization will then happen automatically. Conversely, from these new insights into the mechanism of pore formation can be concluded that apoptosis can be prevented when drugs force the dismantling of the Bax-dimers into their individual elements.
Yamunadevi Subburaj, Katia Cosentino, Markus Axmann, Esteban Pedrueza-Villalmanzo, Eduard Hermann, Stephanie Bleicken, Joachim Spatz and Ana J. García-Sáez: Bax monomers form dimer units in the membrane that further self-assemble into multiple oligomeric species. Nature Communications, 14 August 2015, doi:10.1038/ncomms9042.
Professor Dr. Ana J. García-Sáez
University of Tübingen
Interfaculty Institute of Biochemistry
Phone +49 7071 29-73318
Dr. Karl Guido Rijkhoek | idw - Informationsdienst Wissenschaft
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences