Fine-tuning cell death: The new part of the death machines was revealed


Scientists from Walter and Eliza Hall have identified a significant part of the microdrop machines that control the cell death.

The study group, named VDAC2, was critical of the important pro-death protein, called Bax, which investigates deaths that force damaged, diseased or undesired cells to death.

The team also showed that VDAC2 affected the killing of certain cancer cells with anti-cancer agents. The study was published today in the journal natural Communication, led by Dr. Hui-San Chin, Professor David Huang, Dr Mark van Delft and Associate Professor Grant Dewson.


  • The death of cells by the process known as apoptosis is necessary to remove unwanted, damaged or diseased cells and is controlled by a fine protein "machine".
  • Protein Bax is a key part of a cell death machine that is part of a complex that takes the cells to a point of "auxiliary death" with no return.
  • The researchers found a protein called VDAC2 that helps Bax drive apoptosis and can play a role in fine-tuning cancer cell responses to anti-cancer agents.


Apoptotic cell death is critical to the development and maintenance of our body, and the apoptosis-controlling protein machine has had defects in several diseases. False cell death proteins are associated with both cancer development and cancer cell resistance.

The key to the cell death machine is called Bax, Dr. van Delft said. "Bax helps to take the cell to a" non-return point "when apoptotic cell death is triggered, forming pores in mitochondria, cells' power ranges, which liberates the ultimate" killer "proteins that dislodge the cell.

"Understanding how Bax functions could lead to new therapeutic agents that either promote cell death – applications for diseases such as cancer or therapeutic agents that prevent cell death that can save cells in conditions such as neurodegeneration or stroke.

The team explored how Bax and the related protein, called Bak, kill cells that copy the activities of different genes by CRISPR technology, Professor Dewson said.

"To our surprise, we discovered a gene that was essential to Bax's activity but not to Bak, even though these two proteins were functionally and structurally very similar.

"We have been able to follow this study to demonstrate that the protein, called VDAC2, was a catalyst that helped Bax connect with mitochondria and form pores in membranes when killing cells," Professor Dewson said. "Interestingly, VDAC2's" day work "is to maintain mitochondrial activity by pumping metabolites into and out of mitochondria."


The failure of the cell death mechanism is a sign of cancer cells and is associated with cancer cell resistance to cancer treatment, said Professor Huang.

"Bax is important to help anticancer agents kill cells – without Baxia and its relative bacteria, cancer cells can not be met with apoptosis when treated with various anti-cancer treatments.

"Our research showed that Bax must require VDAC2 to direct cancer cell responses to traditional chemotherapeutics as well as to newly developed BH3 mimetics," Professor Huang said.


The research was supported by the Australian National Health and Medical Research Council, the Australian Research Council, the Cancer Council Victoria, the Australian Cancer Research Foundation, the Leukemia and Lymphoma Society (USA), and the Victorian Government. Dr. Hui San Chin received a PhD scholarship from the University of Melbourne.

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