In a deadly double whammy, Bak helps chop the finger-like filament shape of the cell's powerhouse, or mitochondrion, into vulnerable little spheres. Another protein Bax then pokes countless holes in those spheres, spilling their pro-death contents into the cell.
"We found out Bak has a distinct function in regulation of the mitochondrial morphology," says Dr. Zheng Dong, cell biologist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta and corresponding author on a paper published this week in Proceedings of the National Academy of Sciences. "Bax, on the other hand, is not involved in morphological regulation but needs to be there to puncture holes."
"One has to break up, kind of soften, the mitochondria for injury, and the other one actually punches the holes to kill it," says Craig Brooks, MCG graduate student and the paper's first author.
Bak and Bax have similar structures and scientists have long suspected they play major, similar roles in programmed cell death, or apoptosis. "These two proteins are very important for mitochondrial injury and subsequent apoptosis," says Dr. Dong.
To stress cells, they blocked oxygen supplies and used the common chemotherapeutic agent cisplatin, then documented that filamentous mitochondria became fragmented very early and quickly in apoptosis. Ironically they also found the deadly fragmentation results from Bak's interaction with mitochondria-shaping proteins called mitofusins, which help mitochondria keep their filamentous shape in non-stressed cells. Dr. Dong suspects Bak may also play a role in mitofusin regulation in normal, non-stressful conditions.
In fact, the researchers suspect Bak, Bax and the contents they spill into the cell all have roles in keeping a cell functioning until a stressor kicks in.
"They probably are both kept in check normally in the cell by other proteins, and when something happens that overwhelms the cell, it activates Bak and Bax to start cell death," says Mr. Brooks. "Some of the same proteins, cytochrome c is the big one, are needed for daily mitochondrial function like making energy, but if they are released from the mitochondria, they activate a cell killing or apoptotic pathway," says Dr. Dong, referencing the contents that spill from punctured mitochondria.
Looking at kidney cells and neurons in a Bak deficient mouse, they also showed that Bak and Bax need each other to successfully spawn cell suicide. "If you have Bak but not Bax, the mitochondria still fragment but they don't die; if you have Bax but not Bak, you still have punctures in the mitochondria but with low efficiency," says Mr. Brooks.
Now they want to know exactly how Bak interacts with mitofusins, how the interaction is regulated and how it affects mitochondrial morphology, physiology and pathology. Their long-term goal for better understanding the cell suicide mechanism is developing drugs to block it in the case of a stroke, for example, or induce it to kill cancer.
Dr. Dong recently received a $1.1 million, four-year renewal grant from the National Institute of Diabetes & Digestive & Kidney Diseases to further study the structural changes of mitochondria during apoptosis and normal physiological conditions.
Toni Baker | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
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...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences