Ferroptosis as A New Cell Death

Yıl 2021, Cilt: 30 Sayı: 4, 258 - 268, 30.12.2021

Alper Çelenk

https://doi.org/10.17827/aktd.980659

Cited By: 2

Öz

Ferroptosis is a newly discovered cell death form originates from iron-dependent lipid peroxide accumulation, which differs from traditional apoptosis and necrosis. This is characterized by cytological changes including cell death, shrinkage of cell volume and increased mitochondrial membrane density. Morphologically, mitochondrial membrane condensation, impairment or destruction of the mitochondria crista, and mitochondrial membrane rupture, and smaller mitochondria than normal mitochondria can be seen. Ferroptosis can be induced by class of two small molecule substances known as class 1 and class 2 ferroptosis inducers. In addition to these substances, it can also be induced by drugs such as Sorafenib and artemisine derivative. In cancer cells and some normal cells, such as renal tubule cells, it can be triggered by these drugs and class 1 and 2 ferroptosis inducers. Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, increased endoplasmic reticulum stress, and inhibition of the cystine-glutamate delivery system have been implicated in the induction of ferroptosis. This process is caused by the accumulation of lipid peroxidation products and reactive oxygen species (ROS) derived from iron metabolism. Ferroptosis may be inhibited by iron chelators (eg, Deferoxamine) and lipid peroxidation inhibitors (eg, Ferrostatin). Ferroptosis plays an undeniable role in the proliferation of some tumor cells such as lymphocytoma, pancreatic ductal cell cancer, renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).

Anahtar Kelimeler

Cell death, ferroptoz, lipid peroxidation, reactive oxygen species, iron chelators.

Yeni Bir Hücre Ölüm Şekli Olarak Ferroptozis

Öz

Ferroptozis, geleneksel apoptoz ve nekrozdan farklılık gösteren, demir bağımlı lipid peroksit birikiminden kaynaklanan ve yeni keşfedilen bir hücre ölüm şeklidir. Bu hücre ölümü, hücre hacminin küçülmesi ve artan mitokondriyal membran yoğunluğu dahil olmak üzere sitolojik değişiklikler ile karakterize edilmektedir. Morfolojik olarak, mitokondriyal membran yoğunlaşması ve ruptürü, mitokondriyon kristalarının küçülmesi veya yok olması ile mitokondri normalden daha küçük görülebilir. Ferroptozis, sınıf 1 ve sınıf 2 ferroptozis indükleyiciler olarak bilinen iki küçük molekül sınıfı ile indüklenebilir. Bu moleküllere ek olarak sorafenib ve artemisin türevi ilaçlar tarafından da uyarılabilmektedir. Kanser hücrelerinde ve böbrek tübül hücreleri gibi bazı normal hücrelerde, bu ilaçlar ve sınıf 1 ve 2 ferroptozis indükleyiciler ile ferroptozis tetiklenebilmektedir. Mitokondriyal voltaj bağımlı anyon kanallarının ve mitojen ile aktive olan protein kinazların aktivasyonu, endoplazmik retikulum stresinin artması ve sistin-glutamat taşıma sisteminin inhibisyonu da ferroptozisin indüklenmesinde rol oynamaktadır. Bu durum, demir metabolizmasından türetilen lipit peroksidasyon ürünlerinin ve reaktif oksijen türlerinin (ROS) birikmesi ile oluşmaktadır. Ferroptozis, demir şelatörler (örn., Deferoksamin) ve lipid peroksidasyon inhibitörleri (örn., Ferrostatin) tarafından inhibe edilebilir. Ferroptozis, lenfositoma, pankreas duktal hücre kanseri, renal hücreli karsinoma (RCC) ve hepatosellüler karsinoma (HCC) gibi bazı tümör hücrelerinin proliferasyonunda etkin bir rol oynamaktadır.

Anahtar Kelimeler

Hücre ölümü, Ferroptozis, lipid peroksidasyonu, reaktif oksijen türleri, demir şelatörler

Kaynakça

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