Characterizing the Regulation of Ferroptosis

项目摘要 铁下垂是一种铁依赖的氧化性细胞死亡途径，与肿瘤抑制有关 以及病理性细胞死亡。这一过程在生物化学上有别于细胞凋亡，即典型的坏死。 以及铁超载导致的细胞死亡。铁下垂是如何在分子水平上被调控的尚不清楚。 明白了。在初步数据的指导下，这项研究将检验铁下垂是 受雷帕霉素(MTOR)信号转导和中性脂质合成机制的调控。 此外，使用现有的和新发现的抗氧化剂抑制剂进行的成像研究 铁下垂将精确定位致命的铁依赖的脂质活性氧物种的细胞位置。 铁性下垂期间的(ROS)积聚，并检查mTOR如何影响这种积聚 信号和中性脂肪合成。这些研究将在人类细胞中进行，并得到帮助 一种新的延时细胞死亡成像系统和来自化学生物学的技术， 遗传学和生物化学。这项研究将促进人们对铁性下垂的认识。 分子和细胞水平，为今后的体内研究奠定了基础 了解细胞死亡过程。

Project Abstract Ferroptosis is an iron-dependent, oxidative cell death pathway implicated in tumor suppression and pathological cell death. This process is biochemically distinct from apoptosis, classic necrosis and iron overload-induced cell death. How ferroptosis is regulated at the molecular level is poorly understood. Guided by preliminary data, this research will test the hypotheses that ferroptosis is regulated by mechanistic target of rapamycin (mTOR) signaling and neutral lipid synthesis. Moreover, imaging studies using existing and newly discovered antioxidant inhibitors of ferroptosis will pinpoint the cellular sites of lethal iron-dependent lipid reactive oxygen species (ROS) accumulation during ferroptosis and examine how this accumulation is affected by mTOR signaling and neutral lipid synthesis. These studies will be performed in human cells with the aid of a novel time-lapse cell death imaging system and techniques drawn from chemical biology, genetics and biochemistry. This research will advance the understanding of ferroptosis at the molecular and cellular levels and lay the foundation for future in vivo studies of this poorly understood cell death process.