Researchers at the VIB-KU Leuven Center on Cancer Biology have revealed how a unique interaction between two cellular apartments, namely the endoplasmic network (ER) and the mitochondria, can act as a central ignition point for piercing, a form of cellular death. In a study published in Biology of Nature CellProfessor Patrizia Agostinis’s team highlights the role of ER-Mitochondria (EMCSS) contact areas in starting a waterfall leading to the death of cancer cells.
Fencing is a type of cell death that occurs when some fats (called phospholipids or PLs) in cell membranes are destroyed by oxidation, as a consequence of the exclusion of the main defense system of the cell. This damage is known as lipid peroxidation and is a key feature of iron. Once the lipid peroxidation begins, it quickly spreads to the outer layer of the cell, destroying the main obstacle and leading to cell death. Ferry is a recently discovered way that causes cell death and has been linked to the development and development of various diseases, such as neurodegenerative disorders and cancer. However, to this day, where the peroxidation of the PL cell begins, it remains unknown.
In a study led by Professor Patrizia Agostinis of Vib-Ku Leuven Center for Cancer Biology, live super resolution was used for the arrangement of spatial events caused by iron-level iron events. The research team watched the exact moment of peroxides PL and spread into the cell. They found that the first cell membranes that are susceptible to lipid peroxidation are intra-meth-of-network contact positions (EMCS). The EMCSS not only extends rapidly in response to lipid peroxidation, but it also plays a key role in the dissemination of catastrophic lipids in mitochondria. In turn, this causes an increase in the production of reactive oxygen species (ROS) and fragmentation of these organic organic organic, which enhances cellular damage.
Maria Livia Sassano, first author of the study: “Our findings show that EMCSS, due to their specific lipid landscape, act as operational administration centers for the start and dissemination of lipid peroxidation to cells undergoing.
Enhance the iron to beat cancer cells
Having discovered the role of EMCSS in iron deficiency, the researchers found that by disturbing the physical relationship between the endoplasmic network and the mitochondria significantly reduced the accumulation of harmful lipid peroxides. This “unused” effect effectively runs the cells from submitting iron. Reversely, reinforcing and stabilizing ER-Mitochondria connections intensifies peroxidation PL and accelerates cell death
Based on these findings, the study shows that strengthening EMCs could be an effective strategy to enhance the vulnerability of aggressive tumors, such as the triple negative breast cancer (TNBC). TNBC tumors do not react in the same way to treatment, causing iron. Those who of course have more EMCs are particularly vulnerable to ironing, while TNBC in which ER and mitochondria are not in good contact is more difficult to kill, but can raise awareness by forcing these organs to come close. Playing in this advantage, scientists can increase the sensitivity of the tumor to lipid damage, effectively inhibiting the balance to this type of cell death.
“Our findings may have relevant consequences for TNBC, resistant to cancer hormones that are much more difficult to treat than other types of breast cancer, as the” EMCS state “could serve as a biomarker of the vulnerability of these tumors in the treatments that cause iron -caused iron. Explains Professor Patrizia Agostinis of Vib-Ku Leuven Center for Cancer Biology. “In a more general note, with this new fundamental knowledge, we can begin to design strategies that are specifically targeted and shape these cell hotspot.
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Magazine report:
Sassano, ml, et al. (2025). Endoplasmic contacts -Mitocondria are primary points of phospholipid peroxidation leading to iron. Biology of Nature Cell. Doi.org/10.1038/S41556-025-01668-Z.
