Bak protein sets stressed cells on suicide path, researchers show

Jul 12, 2007
Bak Protein Sets Stressed Cells on Suicide Path, Researchers Show
Cell image: The control cell has normal, filamentous mitochondria while the stressed, dying cell has numerous mitochondrial fragments. Credit: Medical College of Georgia

When a cell is seriously stressed, say by a heart attack, stroke or cancer, a protein called Bak just may set it up for suicide, researchers have found.

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. Dhong, 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.

Source: Medical College of Georgia

Explore further: New compounds protect nervous system from the structural damage of MS

add to favorites email to friend print save as pdf

Related Stories

Breakthrough in OLED technology

29 minutes ago

Organic light emitting diodes (OLEDs), which are made from carbon-containing materials, have the potential to revolutionize future display technologies, making low-power displays so thin they'll wrap or fold ...

An old-looking galaxy in a young universe

29 minutes ago

A team of astronomers, led by Darach Watson, from the University of Copenhagen used the Very Large Telescope's X-shooter instrument along with the Atacama Large Millimeter/submillimeter Array (ALMA) to observe ...

Genetically speaking, mammals are more like their fathers

30 minutes ago

You might resemble or act more like your mother, but a novel research study from UNC School of Medicine researchers reveals that mammals are genetically more like their dads. Specifically, the research shows ...

Recommended for you

Team finds key to tuberculosis resistance

3 hours ago

The cascade of events leading to bacterial infection and the immune response is mostly understood. However, the molecular mechanisms underlying the immune response to the bacteria that causes tuberculosis ...

Mutation may cause early loss of sperm supply

4 hours ago

Brown University biologists have determined how the loss of a gene in male mice results in the premature exhaustion of their fertility. Their fundamental new insights into the complex process of sperm generation ...

No more bleeding for 'iron overload' patients?

6 hours ago

Hemochromatosis (HH) is the most common genetic disorder in the western world, and yet is barely known. Only in the US 1 in 9 people carry the mutation (although not necessarily the disease).

3-D printing offers innovative method to deliver medication

11 hours ago

3-D printing could become a powerful tool in customizing interventional radiology treatments to individual patient needs, with clinicians having the ability to construct devices to a specific size and shape. That's according ...

Mystery of the reverse-wired eyeball solved

Feb 27, 2015

From a practical standpoint, the wiring of the human eye - a product of our evolutionary baggage - doesn't make a lot of sense. In vertebrates, photoreceptors are located behind the neurons in the back of the eye - resulting ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.