OXIDATIVE PHOSPHORYLATION IN CELL GROWTH AND DEATH

描述(改编自调查人员摘要)：PI建议研究 线粒体DNA氧化磷酸化缺陷在两个方面的影响 癌症的威胁。 主要有两个目标：第一，确定OXPHOS缺陷在细胞中的作用 第二，决定OXPHOS缺陷的作用 在细胞死亡中。背景是体细胞线粒体DNA突变 在许多结直肠肿瘤中都有描述。然而，它们在肿瘤生长中的作用并不是 明白了。他计划使用三种携带mtDNA的结直肠癌细胞系 突变作为模型来研究mtDNA突变的表型后果。这个 这些细胞系的线粒体DNA将被转移到骨肉瘤细胞系 如果没有mtDNA，对线粒体功能和细胞生长的影响将 被评估。这些和其他线粒体DNA突变对OXPHOS的影响 体外和体内的活性氧产生、细胞生长和细胞凋亡 将对活体进行检查。在第二个具体目标中，他将研究 线粒体功能障碍对细胞凋亡的基因决定作用。骨肉瘤 带有和不带有线粒体DNA的细胞系将被用来检验Low的影响 线粒体膜电位和氧磷脂受损在易感性中的作用 细胞凋亡。不同mtDNA环境对Bclxl和Bax表达的影响 还将接受检查。

DESCRIPTION (Adapted from investigator's abstract): The PI proposes to study the effects of mtDNA oxidative phosphorylation (OXPHOS) defects in two aspects of cancer. There are two main goals: First, determine the role of OXPHOS defects in cell growth and tumor development; and second, determine the role of OXPHOS defects in cell death. The background is that somatic mtDNA mutations have been described in many colorectal tumors. However, their role in tumor growth is not understood. He plans to use three colorectal cancer cell lines with mtDNA mutations as models to study the phenotypic consequence of mtDNA mutations. The mtDNA from these cell lines will be transferred to an osteosarcoma cell line without mtDNA, and the effects on mitochondrial function and cell growth will be assessed. The effects of these and other mtDNA mutations in OXPHOS on reactive oxygen species production, cell growth, and apoptosis in vitro and in vivo will be examined. In a second specific aim, he will study the effect of genetically determined mitochondrial dysfunction on apoptosis. Osteosarcoma cell lines with and without mtDNA will be used to examine the effects of low mitochondrial membrane potential and impaired OXPHOS on susceptibility to apoptosis. The effects of Bcl-XL and Bax expression in differing mtDNA contexts will also be examined.