BAX – THE CELL SUICIDE MEDIATOR

Apoptosis

Apoptosis is essentially a form of programmed cell death, or ‘cell suicide’. It is an orderly process, in which a controlled routine is followed that leads to the contents of the cell being packaged into small packets of membrane, for collection by immune cells. No harmful substances are released, and the process plays a pivotal role in the development and homeostasis of adult tissues.

However, the process does not always go to plan.

Disruption of the mechanism can have devastating consequences, in the form of cancer or brain disease, yet until recently there has been a lack of comprehensive research and knowledge into the structure of the cells which regulate the operation.

Scientific Context of BAX

BAX is a proapoptotic (regular of apoptosis) protein, of the BCL2 protein family. In order to truly understand the role of the protein, the apoptosis process must be examined in more detail. There are two activation mechanisms of cell death – the intrinsic pathway, and the extrinsic pathway.

In the first, the release of proteins from the intermembrane space of the mitochondria control cell death, and in the latter, extracellular molecules bind to cell surface death receptors, consequently creating the DISC – the death-inducing signalling complex. The protein under the microscope at this very moment, BAX, is concerned with the first, intrinsic activation method of cell suicide.

Role of BAX

BAX is an entity, that as discussed, is involved with the release of proteins from the the membrane of the mitochondria. More specifically, it does this by enhancing the opening of the mitochondrial voltage-dependent anion channel, consequently causing the membrane potential of cells to die down (membrane potential being the potential difference across the cell).

In simpler terms, the protein pierces the outer membrane of the mitochondria, and in doing so mediates cell death. Despite this being confirmed, the arrangement of BAX in cells, and how the protein porates (create holes in) the membrane are far from being fully understood.

New Developments

Very recently, new insights into the cell killer BAX have been uncovered. One of the reasons it was so difficult to do this is because the location of the protein within the cell is always changing. Despite this, researchers at the Ruhr-Universität Bochum and the University of Tübingen have carved out new inroads into understanding the structure of the protein. By analysing how the protein interacts with membrane-like substances e.g. solvents such as water and lipids, a new structural model of the protein has been created.

Why is this important to the future of medicine?

As previously discussed, apoptosis is not simply a process that occurs without any issues. Neurodegenerative diseases i.e. diseases concerned with neuron loss in the brain e.g. Alzheimer’s or Parkinson’s are clearly linked to problems in the mechanisms of the cell suicide process. However, by utilising a higher level of extensive research into the molecular biology of the concept, scientists can gain an even deeper understanding of exactly how apoptosis works. The hope is that in the future, this understanding will allow doctors to better treat the diseases that this process can sometimes cause.

Saeyon Nanthakumar

Photo Credits due to: Saeyon Nanthakumar