生命科学与医学奖
2006

人体由上万亿个细胞组成。每天有上十亿个细胞凋亡并由新生细胞所取代。细胞的生成和凋亡必须精确地平衡。如果细胞生成太多，器官就会长大成为癌，反之，器官将退化，引起如阿尔滋海默症这样的病变。控制细胞生成的因子已经研究了许多年，并且已经了解得很多。相反，直到豪尔维兹揭示蛔虫有一个称为细胞按程序凋亡，由基因决定的控制机制以前，人们认为细胞凋亡是无序的。虽然知道了这个现象，可是直到王晓东证明它是由细胞器―线粒体―执行的以前，细胞按程序凋亡的生物化学机制是不清楚的。过去，人们认为线粒体的功能只是一个能量发生器。

每一个有细胞核的动物细胞都有许多线粒体。线粒体是一个由膜组成的微小的结构，充满了氧化食品和生成高能化合物的酶。当细胞按程序凋亡时，线粒体释放触发细胞凋亡的一些蛋白，其中之一是细胞色素C。长久以来，人们只知道细胞色素C是产能系统必要的成份。王晓东用了聪明的生物化学方法，证明由线粒体来的细胞色素 C 触发一联串反应，导致细胞核脱氧核糖核酸碎裂，细胞膜溶解以及凋亡的细胞被邻近的清扫细胞所吞噬。为了遏制细胞色素C的自杀作用，细胞产生阻遏caspase活力的蛋白。王晓东证明线粒体释放另外一种蛋白，使细胞凋亡得以完成。

The human body is composed of 10 trillion cells. Each day billions of cells die and are replaced by fresh cells. The birth and death of cells must be perfectly balanced. If cell birth exceeds death, organs enlarge and cancer results. If death exceeds birth, organs degenerate, as in Alzheimer’s disease. The factors controlling cell birth have been studied for many decades and much has been learned. In contrast, cell death was considered a random event until the studies of Horvitz in roundworms revealed a gene-determined control mechanism called programmed cell death. Although the phenomenon was recognized, the biochemical mechanism was obscure until Xiaodong Wang showed that the executioner is an internal organelle, the mitochondrion, which was previously thought to function only as an energy generator.

Every nucleated animal cell contains many mitochondria, which are tiny membrane-bound structures filled with enzymes that oxidize foodstuffs and generate high-energy chemicals. When a cell is programmed to die, the mitochondria release proteins that trigger cell death. One such protein, cytochrome C, was long known as an essential component of the energy-generating system. Using clever biochemical measurements, Wang showed that mitochondria-derived cytochrome C binds to a cytosolic protein, Apaf-1, thereby activating a protease called caspase-3. Activated caspase 3 triggers a cascade of reactions that lead to fragmentation of nuclear DNA, dissolution of the cell membrane, and engulfment of the dying cell by neighboring scavenger cells. Cells resist the suicidal action of cytochrome C by producing proteins called IAPs that block the caspase. Wang showed that mitochondria overcome this resistance by releasing another protein, Smac, which neutralizes the IAPs, permitting cell death to proceed to completion. Wang also discovered a mitochondria-derived nuclease that assists in the fragment of nuclear DNA.