Caught in the act: Researchers capture key moments in cell death

Feb 02, 2013
Dr. Peter Czabotar (left) and Dr. Dana Westphal for the first time visualized the molecular changes in a critical cell death protein that force cells to die. Credit: The Walter and Eliza Hall Institute, Australia

Scientists at the Walter and Eliza Hall Institute have for the first time visualised the molecular changes in a critical cell death protein that force cells to die.

The finding provides important insights into how cell death occurs, and could lead to new classes of medicines that control whether live or die.

Cell death, called apoptosis, is important for controlling the number of in the body. Defects in cell death have been linked to the development of diseases such as cancer and neurodegenerative conditions. Insufficient cell death can cause cancer by allowing cells to become immortal while excessive cell death of neurons may be a cause of .

Dr Peter Czabotar, Professor Peter Colman and colleagues in the institute's division, together with Dr Dana Westphal from the institute's Molecular Genetics of Cancer division, made the discovery which is published in the latest edition of the journal Cell.

Dr Czabotar said activation of the protein Bax had long been known to be an important event leading to apoptosis, but until now it was not known how this activation occurred. "One of the key steps in cell death is that holes are punched into a membrane in the cell, the mitochondrial membrane," Dr Czabotar said. "Once this happens the cell is going to go on and die. Bax is responsible for punching the holes in the mitochondrial membrane and visualising its activation brings us a step closer to understanding the mechanics of cell death."

This video is not supported by your browser at this time.
Dr. Peter Czabotar of the Walter and Eliza Hall Institute, Australia, discusses his discovery of how a key molecule, Bax, changes its shape to drive cell death. Credit: The Walter and Eliza Hall Institute, Australia

Using the Australian Synchrotron, Dr Czabotar and colleagues were able to obtain detailed of Bax as it moved from its inactive to active form. The active form ruptures mitochondrial membranes, removing the cell's energy supply and causing cell death.

"By using the powerful X-ray beams created by the synchrotron, we obtained structures of Bax that were really exciting," Dr Czabotar said. "Bax is activated when small protein fragments called BH3-peptides bind to it. We saw that these peptides open up the Bax molecule like a key unlocking a padlock. This unlocked form of Bax can bind to another Bax molecule, which can then form larger Bax complexes that can go on to break up membranes in the cell.

"As well as explaining the detail of how cell death occurs, our research could provide clues about how to design potential new therapeutic agents that target Bax," Dr Czabotar said. "Now that we can see how Bax changes its shape to move from the inactive to the active form, it may be possible to block Bax activation, to prevent cell death in conditions such as neurodegenerative disorders, where illness is caused by excessive . Similarly, agents that drive Bax into its active form could force immortal cells such as cancer cells to die, providing the basis for a potential new class of anti-cancer agents."

Explore further: How plant cell compartments change with cell growth

Related Stories

Immune cell death defects linked to autoimmune diseases

Jan 23, 2013

Melbourne researchers have discovered that the death of immune system cells is an important safeguard against the development of diseases such as type 1 diabetes, rheumatoid arthritis and lupus, which occur ...

Key protein that may cause cancer cell death identified

Jan 16, 2009

Researchers at A*STAR's Institute of Molecular and Cell Biology (IMCB) have become the first to discover and characterize a human protein called Bax-beta (Baxβ), which can potentially cause the death of cancer cells ...

New strategy directly activates cellular 'death protein'

May 31, 2012

Researchers at Dana-Farber/Children's Hospital Cancer Center have devised a strategy to directly activate a natural "death" protein, triggering the self-destruction of cells. They say the development could represent a new ...

Cell death pathway linked to mitochondrial fusion

Jan 24, 2011

New research led by UC Davis scientists provides insight into why some body organs are more susceptible to cell death than others and could eventually lead to advances in treating or preventing heart attack or stroke.

Recommended for you

How plant cell compartments change with cell growth

Aug 22, 2014

A research team led by Kiminori Toyooka from the RIKEN Center for Sustainable Resource Science has developed a sophisticated microscopy technique that for the first time captures the detailed movement of ...

Plants can 'switch off' virus DNA

Aug 22, 2014

A team of virologists and plant geneticists at Wageningen UR has demonstrated that when tomato plants contain Ty-1 resistance to the important Tomato yellow leaf curl virus (TYLCV), parts of the virus DNA ...

A better understanding of cell to cell communication

Aug 22, 2014

Researchers of the ISREC Institute at the School of Life Sciences, EPFL, have deciphered the mechanism whereby some microRNAs are retained in the cell while others are secreted and delivered to neighboring ...

A glimpse at the rings that make cell division possible

Aug 22, 2014

Forming like a blown smoke ring does, a "contractile ring" similar to a tiny muscle pinches yeast cells in two. The division of cells makes life possible, but the actual mechanics of this fundamental process ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Whydening Gyre
1 / 5 (3) Feb 03, 2013
Interesting research. Wonder if it may have some collateral relevance to Beth Levine's work with Beclin 1.