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!
The body's street sweepers
18.12.2017 | Ludwig-Maximilians-Universität München
Life on the edge prepares plants for climate change
18.12.2017 | Max-Planck-Institut für Entwicklungsbiologie
A study carried out by an international team of researchers and published in the journal Physical Review X shows that ion-trap technologies available today are suitable for building large-scale quantum computers. The scientists introduce trapped-ion quantum error correction protocols that detect and correct processing errors.
In order to reach their full potential, today’s quantum computer prototypes have to meet specific criteria: First, they have to be made bigger, which means...
Since 2016, German and Spanish researchers, among them scientists from the University of Göttingen, have been hunting for exoplanets with the “Carmenes”...
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
18.12.2017 | Life Sciences
18.12.2017 | Materials Sciences
18.12.2017 | Life Sciences