Richter C, Schweizer M, Cossarizza A, Franceschi C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
FEBS Lett. 1996 Jan 8;378(2):107-10. doi: 10.1016/0014-5793(95)01431-4.
Apoptosis is a physiological form of cell death. Its causes and execution mechanisms are not clearly understood. Oxidative stress, nitric oxide and its congeners, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. At present their importance and exact role are elusive but it is clear that mitochondria are both the target and the source of oxidative stress, nitric oxide, and Ca2+. The mitochondrial membrane potential (delta psi), which is the driving force for mitochondrial ATP synthesis, declines during apoptosis, and maintenance of delta psi prevents apoptosis. Since apoptosis is highly regulated and involves the activity of hydrolytic enzymes, chromatin condensation and vesicle formation apoptosis is likely to have a high energy demand. We propose that the cellular ATP level is an important determinant for cell death. This hypothesis is supported by circumstantial evidence, is consistent with the available data, has a corrolary in aging, and is amenable to direct experimental testing particularly with flow cytometry as a promising tool.
细胞凋亡是一种生理性细胞死亡形式。其病因和执行机制尚不清楚。氧化应激、一氧化氮及其同类物、Ca2+、蛋白酶、核酸酶和线粒体被认为是细胞凋亡的介质。目前它们的重要性和确切作用尚不清楚，但很明显线粒体既是氧化应激、一氧化氮和Ca2+的靶点，也是其来源。线粒体膜电位（δψ）是线粒体ATP合成的驱动力，在细胞凋亡过程中会下降，维持δψ可防止细胞凋亡。由于细胞凋亡受到高度调节，涉及水解酶的活性、染色质浓缩和囊泡形成，细胞凋亡可能对能量有很高的需求。我们认为细胞内ATP水平是细胞死亡的一个重要决定因素。这一假设得到了间接证据的支持，与现有数据一致，在衰老过程中有相应的推论，并且特别适合用流式细胞术作为一种有前景的工具进行直接实验测试。
