Study provides molecular mechanism for preventing cancer

Researchers have discovered a key element in cell death that stops cancer from spreading through a unique molecular mechanism in the early stages of the disease. The study is published in the journal Science Advances. The study was conducted with Dr Luke Clifton of the STFC ISIS Neutron and Muon Source (ISIS) in Oxfordshire, co-lead Professor Gerhard Groepner of Ume University and colleagues from the European Spallation Source in Sweden. This is the latest in a series of collaborations by this group to investigate cellular proteins that trigger apoptosis.

Apoptosis is essential for human survival, and its disruption results in carcinogenesis, where cancer cells proliferate and fail to respond to cancer therapy. It is regulated by two proteins with opposing functions called Bax and Bcl-2 in healthy cells. The soluble Bax protein is responsible for eliminating old or diseased cells, and when activated, it creates pores that pierce the mitochondrial membrane of cells and trigger programmed cell death. This can be compensated for by Bcl-2, which is embedded in the mitochondrial membrane and acts to prevent premature cell death by sequestering and sequestering Bax proteins.

Cancer In cancer cells, the pro-survival protein Bcl-2 is overproduced, leading to unrestricted cell proliferation. Although this process has long been understood to be important for the development of cancer, the precise role of Bax and the mitochondrial membrane in apoptosis has been unclear until now. Dr Luke Clifton, STFC ISIS Neutron and Muon Source Scientist and co-lead author, explained, „This work has advanced our knowledge of fundamental mammalian cell processes and opened up exciting possibilities for future research. Understanding how things work when cells work properly. In cancer cells It’s an important step toward understanding what’s going wrong, so it opens the door to potential treatments.”

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The team used a technique called neutron reflectometry (conducted using advanced ISIS SURF and OFSPEC instruments), which enabled them to study how Bax interacts with lipids in the mitochondrial membrane. This built on their previous studies of membrane-bound Bcl-2. Using neutron reflectivity measurements at SURF and OFFSPEC, they were able to study in real time how the protein interacts with lipids in the mitochondrial membrane during the early stages of apoptosis. Using deuterium-isotope labeling, they determined for the first time that when Bax forms pores, it extracts lipids from the mitochondrial membrane and forms lipid-Bax clusters on the mitochondrial surface.

Using time-resolved neutron reflectivity measurement combined with surface infrared spectroscopy at the ISIS Biolab, they were able to see that this pore formation occurred in two stages. The initial rapid adsorption of Bax to the mitochondrial membrane surface occurred simultaneously followed by the slow formation of membrane-dissolving pores and Bax-lipid clusters. This slow permeation process occurred on time scales of several hours, comparable to cell death. This is the first time scientists have found direct evidence for the involvement of mitochondrial lipids during membrane perturbation in cell death initiated by Bax proteins.

Dr. Luke Clifton added, „As far as we can tell, this mechanism by which Bax initiates cell death has not been seen before. As we learn more about the interaction between Bax and Bcl-2 and how it relates to this mechanism, we will have a more complete picture of a process fundamental to human life. . This work really shows the capabilities of neutron reflectivity measurement in structural studies of membrane biochemistry.” The discovery builds on the team’s previous studies on the molecular mechanism of membrane-bound Bcl-2 to inform a more complete understanding of the early stages of apoptosis.

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Umea University scientist and co-lead author Prof. Gerhard Grobner said, „The unique findings here will not only have a significant impact on the field of apoptosis research, but will also open gateways to exploring Bax and its relatives as interesting targets in cancer therapy, such as improving their cell-killing ability.” (ANI)

(This story was not edited by DevDiscourse staff and was generated automatically from a syndicated feed.)

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