CAJ | 학술논문

背景叉头框蛋白O类(forkhead box protein O,FOXO)3a转录因子是细胞凋亡和细胞周期的调节者,也调控细胞生存或活性氧簇(reactive oxygen species,ROS)生成.目的阐述FOXO3a激活对细胞线粒体呼吸作用的调控,进一步说明FOXO3a是细胞应激的信息整合因子和细胞稳态的主要调控因子.内容讨论FOXO3a转录因子在调节细胞稳态中的作用,重点在线粒体完整性、形态和活性.在神经肿瘤细胞中,FOXO3a诱发ROS积聚,短暂性增加线粒体外膜通透性,这对FOXO3a诱发凋亡是关键的.细胞ROS水平受FOXOa靶因子Bcl-2 interacting mediator of cell death (BIM)、B-cell lymphomaextra large(BCL-XL)和生存素影响.这3个蛋白定位于线粒体并影响线粒体膜电位、呼吸和细胞ROS水平.FOXO3a激活BIM引起线粒体去极化,引起细胞呼吸和ROS产生短暂性降低.趋向 FOXO3a调控线粒体ROS的产生和解毒过程间的动态平衡,在细胞死亡过程中具有重要作用.
배경 차두광단백O류(forkhead box protein O,FOXO)3a전록인자시세포조망화세포주기적조절자,야조공세포생존혹활성양족(reactive oxygen species,ROS)생성.목적 천술FOXO3a격활대세포선립체호흡작용적조공,진일보설명FOXO3a시세포응격적신식정합인자화세포은태적주요조공인자.내용 토론FOXO3a전록인자재조절세포은태중적작용,중점재선립체완정성、형태화활성.재신경종류세포중,FOXO3a유발ROS적취,단잠성증가선립체외막통투성,저대FOXO3a유발조망시관건적.세포ROS수평수FOXOa파인자Bcl-2 interacting mediator of cell death (BIM)、B-cell lymphomaextra large(BCL-XL)화생존소영향.저3개단백정위우선립체병영향선립체막전위、호흡화세포ROS수평.FOXO3a격활BIM인기선립체거겁화,인기세포호흡화ROS산생단잠성강저.추향 FOXO3a조공선립체ROS적산생화해독과정간적동태평형,재세포사망과정중구유중요작용.
Background Forkhead box O (FOXO) 3a transcription factors are regulators of cell-type specific apoptosis and cell cycle arrest,but also control cell survival and production of reactive oxygen species(ROS).Objective To review the FOXO3a self-reactivating loop and novel functions of FOXO3a in controlling mitochondrial respiration of cells,which further supports the current view that FOXO3a transcription factors are information-integrating sentinels of cellular stress and critical modulators of cell homeostasis.Content In this article,we will discuss the current knowledge on the involvement of FOXO3a transcription factors in the regulation of cellular homestasis with specific emphasis on mitochondrial integrity,morphology and activity.In neuronal tumor cells,FOXO3a triggers ROS-accumulation as a consequence of transient mitochondrial outer membrane permeabilization,which is essential for FOXO3a-induced apoptosis in these cells.Cellular levels of reactive oxygen species are affected by the FOXO3a-targets including Bim,BclxL,and Survivin.All three proteins localize to mitochondria and affect mitochondrial membrane potential and respiration,as well as cellular levels of reactive oxygen species.Trend FOXO3a controls a delicate balance between mitochondrial reactive oxygeu species-generation and levels of reactive oxygen species-preventing or detoxifying processes,which is critical for cell death decision in neuronal cells.