Cytochrome P450 Derived Metabolites of Arachidonic Acid Differentially Regulate Cell Death Pathways

线粒体是一种几乎存在于每个细胞中的结构。线粒体的主要功能是将能量转化为细胞可用的形式。细胞使用这种能量来完成生存和功能所必需的特定工作。此外，线粒体在启动导致细胞死亡事件的信号中起着至关重要的作用。因此，线粒体是调节细胞死亡和存活的关键成分（细胞器）。这些动态细胞器经历了持续的伸长和断裂过程，以维持正常的功能和满足细胞的需求。基因异常、疾病或毒性引起的这些过程的严重破坏会影响细胞的能量产生。这可能导致细胞功能障碍和死亡。花生四烯酸（AA）是一种存在于细胞膜上的分子，在激素和细胞应激等刺激下会释放出来。细胞内的蛋白质将其分解成活性分子，称为环氧二十碳三烯酸（EETs）和羟基二十碳四烯酸（HETE），它们可以调节身体的各种功能。最近的研究表明，eet和HETE具有相互竞争的作用，其中eet促进细胞存活，HETE促进细胞死亡。我的长期研究计划目标是了解这些分子如何调节线粒体功能和限制损伤。目前的拨款提案研究了eet和HETEs如何调节线粒体功能和能量产生。这项研究的结果将确定新的调控机制，并促进我们对线粒体功能的理解。

Mitochondria are structures that are found in virtually every cell. The main function of mitochondria is to convert energy into forms that are usable by the cell. The cell uses this energy to perform the specific work necessary for survival and function. In addition, mitochondria play a vital role in initiating signals that trigger events leading to cell death. Therefore, mitochondria are key components organelles) of cells that regulate both cell death and survival. These dynamic organelles undergo continuous elongation and fragmentation processes to maintain proper function and meet cellular demands. Significant disruption in these processes caused by genetic abnormalities, disease or toxicity can impact the energy production of the cell. This can result in cellular dysfunction and death. Arachidonic acid (AA) is a molecule found in cell membranes that can be released in response to several stimuli such as hormones and cellular stress. Proteins within a cell break it down into active molecules called epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETE), which can regulate various functions in the body. Recent research has demonstrated that EETs and HETEs have competing effects, where EETs promote cell survival and HETE promote cell death. My long-term research program objectives are to understand how these molecules regulate mitochondrial function and limit injury. The current grant proposal investigates how EETs and HETEs regulate mitochondrial function and energy production. Results from this study will identify new regulatory mechanisms and advance our understanding of mitochondrial function.