Iron is the most abundant transition metal element within organisms and participates in various physiological activities. Recently, free iron in living cells has attracted attention because its high reactivity may be related to cell death called Ferroptosis. Ferroptosis was coined by Stockwell et al. at Columbia University in 2012 and described as a form of iron-dependent cell death.
Ferroptosis is a form of programmed cell death caused by iron ion-dependent accumulation of lipid peroxides. Ferroptosis has been shown to follow a different cell death pathway from apoptosis and thus is attracting attention as a new target for cancer therapy. It has also been found to be associated with various diseases, such as neurodegenerative diseases, cerebral apoplexy, and hepatitis (NASH).
Guillermo Albaiceta et al.’s group found that fibrosis and cellular senescence in mice and humans are characterized by the accumulation of iron. Fibrosis is the pathological condition causing the growth of excess fibrous connective tissue in an organ or body system. On the other hand, cellular senescence is defined as the process by which cultured cells stop proliferating after a finite number of replications and enter a state of cell cycle arrest.
This is thought to be due to the DNA damage response caused by the shortening of telomeres through repeated cell division, which leads to cell cycle arrest. They report that vascular and hemolytic damage efficiently causes iron accumulation. In addition, they found that induced senescence may promote fibrosis.
They delivered free iron intratracheally to mice in a concentration that approximates the estimated local iron concentration of red blood cells (RBCs) immediately after their hemolysis and release of iron from hemoglobin. In addition, iron levels in senescent cells were detected using FerroOrange (#F374 Dojindo) and it was found that intracellular iron increases, which causes high levels of ROS and SASP.
The present study suggests that ferroptosis plays an important role in the pathobiology of fibrosis.
Identify iron metabolism as a potential therapeutic target for senescence-associated diseases, and expect iron measurement to be used in clinical diagnosis for early detection of fibrosis disease.
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Special thanks to our partner from Dojindo Laboratories, JAPAN, for writing this article.
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