Among these forms of nonapoptotic cell death, ferroptosis (derived from the Greek word ptosis, meaning “a fall,” and ferrum, the Latin word for iron) has been first described in 2012 as an iron-dependent form of RCD, which is characterized by the requirement of redox active iron 4. Starting with the recognition of apoptosis, the prime example of “programmed cell death” 2, extensive research performed in recent years has led to identification of a number of regulated necrotic cell death routines, such as necroptosis, netosis, entosis, and cyclophilin D-mediated cell death 3. In contrast to this unregulated form of cell death, nature has evolved a variety of highly controlled cell death modalities (regulated cell death, RCD), which ensure that during normal development and tissue homeostasis the final decision of life versus death is properly orchestrated. Yet under certain conditions, including physical and chemical injuries of the plasma membrane and other cell constituents, cells are unable to control the cell death process, which is therefore commonly referred to as “accidental/explosive” or necrotic cell death. As such, cell death antagonizes all cellular functions, thus representing an equally important mechanism for proper development and tissue homeostasis of multicellular organisms. The term cell death, first mentioned in 1842 1, describes the ultimate ending of all essential cellular processes in living cells.
acyl-CoA synthetase long chain family member 4.
Na +-independent cystine-glutamate antiporter.Additionally, we review early works carried out long time before the term “ferroptosis” was actually introduced but which were instrumental in a better understanding of the role of ferroptosis in physiological and pathophysiological contexts. Hence, this review aims at summarizing recent advances in our understanding to what is known about enzymatic and nonenzymatic routes of lipid peroxidation, the involvement of iron in this process and the identification of novel players in ferroptotic cell death. Although great strides have been made towards a better understanding of the proximate signals of distinctive lipid peroxides in ferroptosis, still little is known about the mechanistic implication of iron in the ferroptotic process. A hallmark of ferroptosis is iron-dependent lipid peroxidation, which can be inhibited by the key ferroptosis regulator glutathione peroxidase 4(Gpx4), radical trapping antioxidants and ferroptosis-specific inhibitors, such as ferrostatins and liproxstatins, as well as iron chelation. Ferroptosis is a recently described form of regulated necrotic cell death, which appears to contribute to a number of diseases, such as tissue ischemia/reperfusion injury, acute renal failure, and neurodegeneration.
0 kommentar(er)
