[논문]새로운 non-apoptotic 세포사멸: ferroptosis

우선민; 권택규

doi:10.12701/yujm.2017.34.2.174

새로운 non-apoptotic 세포사멸: ferroptosis
Novel non-apoptotic cell death: ferroptosis 원문보기

Yeungnam University Journal of Medicine = 영남의대학술지, v.34 no.2, 2017년, pp.174 - 181

우선민 (계명대학교 의과대학 면역학교실) , 권택규 (계명대학교 의과대학 면역학교실)

Abstract ▼ AI-Helper

Ferroptosis is a newly recognized type of cell death that results from iron-dependent lipid peroxidation and is different from other types of cell death, such as apoptosis, necrosis, and autophagic cell death. This type of cell death is characterized by mitochondrial shrinkage with an increased mitochondrial membrane density and outer mitochondrial membrane rupture. Ferroptosis can be induced by a loss of activity of system $X_c{^-}$ and the inhibition of glutathione peroxidase 4, followed by the accumulation of lipid reactive oxygen species (ROS). In addition, inactivation of the mevalonate and transsulfuration pathways is involved in the induction of ferroptosis. Moreover, nicotinamide adenine dinucleotide phosphate oxidase and p53 promote ferroptosis by increasing ROS production, while heat shock protein beta-1 and nuclear factor erythroid 2-related factor 2 inhibit ferroptosis by reducing iron uptake. This article outlines the molecular mechanisms and signaling pathways of ferroptosis regulation, and explains the roles of ferroptosis in human disease.

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문제 정의

본 보고에서는 기존에 알려진 세포사멸과 다른 새로운 형태의 세포사멸인 ferroptosis의 조절 기전과 신호전달경로 및 다양한 질병에서의 역할에 대해 기술하고자 한다.

질의응답

핵심어	질문	논문에서 추출한 답변
	Ferroptosis는 무엇인가?	Ferroptosis는 최근에 발견된 세포사멸(cell death)의 한 종류로, 철(iron) 매개의 지질 과산화(lipid peroxidation)에 의해 유도되는(regulated) 세포사멸이다[1]. 철은 산소 수송과 DNA 생합성 및 ATP 합성에 관여하는 인자로 세포 생존에 매우 중요한 역할을 한다[2,3].
	미토콘드리아에서 활성산소가 과하게 생성되어 일어나는 ferroptosis 과정의 유도물질로는 어떤 것들이 발견되었는가?	이 과정에서 활성산소가 과하게 생성되면 산화적 스트레스(oxidative stress)가증가하고 세포사멸이 일어나는데, 이를 ferroptosis라 한다 [5]. 최초의 ferroptosis 유도제로는 Ras가 돌연변이 형태로 존재하는 암세포에서 세포사멸을 유도하는 erastin이 발견되었고[6], 이후 저분자 물질 스크리닝 기법을 통하여 non-apoptotic 세포사멸을 유도하는 Ras-selective lethal small molecule 3 (RSL3)가 발견되었다[7].
	철은 체내에서 활성 산소를 어떻게 생성하는가?	철은 산소 수송과 DNA 생합성 및 ATP 합성에 관여하는 인자로 세포 생존에 매우 중요한 역할을 한다[2,3]. 철은 체내 포화지방산의 지질 과산화를 유도하며, 미토콘드리아에서 ATP 합성과 함께 활성 산소(reactive oxygen species)를 생성한다[4]. 이 과정에서 활성산소가 과하게 생성되면 산화적 스트레스(oxidative stress)가증가하고 세포사멸이 일어나는데, 이를 ferroptosis라 한다 [5].

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