Researchers at the Vib-Ku Leuven Center for cancer biology have revealed how a unique interaction between two cellular coaches, ie endoplasmic reticulum (ER) and mitochondria, can act as a central ignition point for ferroptosis, which is a form of a formation of the cell death by lipid oxidation and iron. In a study published in Nature cell biologyProfessor Patricia Egostinis’s team highlights the role of ER-Mitochondria contact sites (EMCS) in installing a cascade leading to the death of cancer cells.

Ferroptosis is a type of cell death that occurs when some fat (called phospholipids, or PLS) in the cell membrane is damaged by oxidation as a result of the blockade of the main defense system of the cell. This damage is known as lipid peroxidation and is a major feature of pheroptosis. Once the lipid peroxidation begins, it quickly spreads to the outer layer of the cell, damaging the main obstruction and leading to the cell death. Ferroptosis is a recently discovered method that causes cell death, and has been linked to the development and progression of various diseases, such as neurodygenetrable disorders and cancer. However, till date, where Pl peroxidation begins inside the cell, remains unknown.

In a study led by Patriadia Agostinis, Professor of Vib-Ku Leuven Center for cancer biology, super-regulation live imaging was used to chart spatioPorpral events triggered by ferroptosis at an inter-organ level. The research team tracked the exact moment Pl peroxide form and spread within the cell. They found that the first cellular membrane for lipid peroxidation is the endoplasmic reticulum-mitochondrial contact sites (EMCSS). EMCSS not only expands rapidly in response to lipid peroxidation, but also plays an important role in spreading harmful lipids in mitochondria. In turn, this causes an increase in production of reactive oxygen species (ROS) and fragmentation of these energy-producing organneles, which increases cellular damage.

Maria Livia Sasano, first writer of study: “Our findings suggest that EMCSS, due to their specific lipid landscape, serves as a functional command center to start and promote lipid peroxidation in cells passing through ferruptosis. An exciting discovery because now we understand what Ferroptosis is and we can control it.”

Cancerous

After discovering the role of EMCSS in ferruptosis, researchers found that disrupting the physical link between endoplasmic reticulum and mitochondria reduced the accumulation of harmful lipid peroxide. This “immoral” effect effectively molds cells by undergoing pheroptosis. In contrast, ER-Mightocondria increases and stabilizing, Pl Peroxidation intensifies and cells accelerate death

Construction at these findings, studies suggest that promoting EMCS may be an effective strategy to enhance vulnerability for froptosis of aggressive tumors such as triple-negative breast cancer (TNBC). TNBC tumors do not react in the same way for all treatments, inducting pheroptosis. People who have more EMCs naturally are particularly unsafe for ferruptosis, while TNBCs that ER and Mitochondria are not in good contact are more difficult to kill, but these organels can be sensitive to come close. Playing in this advantage, scientists can increase the sensitivity of the tumor for lipid damage, effectively tied the balance towards cell death.

“TNBC in our findings may be relevant implications for hormone-resistant cancer that are much harder than other breast cancer types, as ‘EMCS status’ can serve as one Biomarker The vulnerability of these tumors for treatments inducting pheroptosis ” Patricia Agostinis, Professor of the Vib-Ku Leuven Center, describes cancer biology. “On a more common note, with this new fundamental knowledge, we can start designing strategies that especially target and modify these cellular hotspots. By doing this, we expect to increase the pheloptosis vulnerability, especially in those tumors which are resistant to current therapy, while on the other hand, lip -paraoxidacies in the current therapy, on the other hand, reduce lippidness and green deaths on the other hand. For,”