91黑料网 team pinpoints where a type of cell death begins
A team at 91黑料网 studying ferroptosis, a form of cell death, have discovered that the process begins deep inside the cell, a finding that could lead to new treatments for cancer and neurodegenerative diseases.
Using antioxidant probes that light up as they are consumed, the team tracked ferroptosis in real time and identified the endoplasmic reticulum (ER) as the key cellular structure where the process first takes hold. Protecting the ER and the lysosome, they found, can halt ferroptosis entirely.
鈥淔erroptosis has therapeutic potential in cancer treatment and neurodegenerative diseases,鈥� said Gonzalo Cosa, professor in 91黑料网鈥檚 Department of Chemistry and senior author on the study. 鈥淏ut until now, we didn鈥檛 know how it starts or propagates. This information is critical toward understanding the action of current ferroptosis inducers and inhibitors.鈥�
鈥淥ur results show that protecting the ER and lysosomes can abort ferroptosis,鈥� said Cosa. 鈥淚n contrast, protecting the outer leaflet of the plasma membranes does not impact ferroptosis evolution.鈥�
Implications for cancer, neurodegenerative disorders
Ferroptosis kills cells by triggering runaway chemical reactions that damage fats in cell membranes. In cancer, deliberately triggering ferroptosis could stop tumour growth. In Alzheimer鈥檚, Parkinson鈥檚 and other conditions, slowing down ferroptosis could protect healthy brain cells.
鈥淯nderstanding the molecular action of new forms of cell death is critical in health,鈥� said Cosa. 鈥淪uch an understanding paves the way for the development of better therapies.鈥�
A new window into cell death
The researchers鈥� custom-built fluorogenic antioxidants acted as beacons, revealing when and where in the cell, lipid damage began. The research work聽offers a powerful new platform to study drugs designed to either block or induce ferroptosis.
鈥淭hese antioxidants further enable enhanced resolution and visualization of the evolution of this form of cell death, providing unprecedented molecular information at the cellular level,鈥� said Cosa.
About the study
Live-cell imaging with fluorogenic radical-trapping antioxidant probes 1 reveals the onset and progression of ferroptosis by Laiyi Xu, Wenzhou Zhang, Juan F. S谩nchez Tejeda, Denys Holovan, Julia McCain, Terri C. Lovell, and Gonzalo Cosa was published in Nature Chemistry.
