OXIDATIVE PHOSPHORYLATION IN CELL GROWTH AND DEATH

细胞色素c在细胞凋亡中的关键作用被广泛接受。然而，对细胞色素c的需求 细胞凋亡体的形成主要是通过体外实验来确定的。在体内，细胞色素c易位从 线粒体到胞浆是细胞凋亡的指示物，但这种关联并不能解决实际 导致细胞凋亡的机制、要求和事件的顺序。细胞色素c的证明 缺乏突变体及其双重作用，阻碍了体内细胞凋亡的要求。 此外，我们和其他人还表明，氧化磷酸化缺陷可以保护细胞免受 因此，重要的是要区分氧化磷酸化效应和 细胞色素c对细胞凋亡体组装的催化作用。 为了更好地定义与内在凋亡机制(线粒体)相关的机制 途径)，我们建议发展和分析细胞色素c缺陷细胞和小鼠。 这些研究对医学和生物学研究的不同领域具有深远的影响，包括 癌症、神经退化和发育。

The key role of cytochrome c in apoptosis is widely accepted. However, the requirement of cytochrome c for apoptosome formation has been defined mostly by in vitro assays. In vivo, cytochrome c translocation from the mitochondria to the cytosol is an indicator of apoptosis, but this association does not address the actual mechanism, requirements and the sequence of events leading to apoptosis. Proof of cytochrome c requirement for in vivo apoptosis has been hampered by the lack of mutants and its dual role. In addition, we and others have also shown that defects in oxidative phosphorylation can protect cells from an apoptotic death Therefore, it is important to differentiate the oxidative phosphorylation effect from the apoptosome assembly catalysis role of cytochrome c. To better define the mechanisms associated with the intrinsic apoptotic mechanism (the mitochondrial pathway), we propose to develop and analyze cytochrome c deficient cells and mice These studies have far reaching implications to different areas of medical and biological research, including cancer, neurodegeneration and development.