Cytochrome c-induced cytosolic nicotinamide adenine dinucleotide oxidation, mitochondrial permeability transition, and apoptosis
Cytochrome c-induced cytosolic nicotinamide adenine dinucleotide oxidation, mitochondrial permeability transition, and apoptosis
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DOI：
10.1016/s0003-9861(02)00687-2
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发表时间：
2003-02-15
影响因子：
3.9
通讯作者：
Lofrumento, NE
中科院分区：
文献类型：
--
作者：
La Piana, G;Marzulli, D;Lofrumento, NE
将催化量的细胞色素c（cyto-c）添加到分离的线粒体的孵育培养基中，促进还原当量从线粒体外还原态的烟酰胺腺嘌呤二核苷酸（NADH）转移到线粒体内的分子氧，该过程与膜电位的产生相关联。这在许多方面模拟了那些细胞凋亡途径的早期阶段，其特征是线粒体膜电位的持续存在，但细胞质-c已经输出到细胞质中。在环孢霉素敏感和钙诱导的线粒体通透性转换（MPT）的细胞C的释放也可以观察到。然而，在MPT中，与线粒体肿胀相关的解偶联呼吸，并且在此之前，膜电位的完全耗散，其不能用ATP添加或任何其他能量来源恢复，被立即激活。所获得的结果和讨论的完整性的线粒体制剂表明，MPT可能是一个凋亡事件的下游，但不是上游的cyto-c释放连接到能量需求的过程。在细胞凋亡的早期阶段，胞质cyto-c参与半胱天冬酶的激活，同时可以促进胞质NADH的氧化，使更多的能量可用于正确执行细胞死亡程序。这一假设与文献中的可用数据并不相反，文献中的数据表明，cyto-c存在于对照和凋亡诱导的培养细胞系的胞质溶胶中。(C)2002 Elsevier Science（美国）。All rights reserved.
A catalytic amount of cytochrome c (cyto-c) added to the incubation medium of isolated mitochondria, promotes the transfer of reducing equivalents from extramitochondrial nicotinamide adenine dinucleotide in its reduced state (NADH) to molecular oxygen inside the mitochondria, a process coupled to the generation of a membrane potential. This mimics in many aspects the early stages of those apoptotic pathways characterized by the persistence of mitochondrial membrane potential but with cyto-c already exported into the cytosol. In cyclosporin-sensitive and calcium-induced mitochondrial permeability transition (MPT) a release of cyto-c can also be observed. However, in MPT uncoupled respiration associated with mitochondrial swelling and preceded by the complete dissipation of the membrane potential which cannot be restored with ATP addition or any other source of energy is immediately activated. The results obtained and discussed with regard to intactness of mitochondrial preparations indicate that MPT could be an apoptotic event downstream but not upstream of cyto-c release linked to the energy-requiring processes. In the early stages of apoptosis cytosolic cyto-c participates in the activation of caspases and at the same time can promote the oxidation of cytosolic NADH, making more energy available for the correct execution of the cell death program. This hypothesis is not in contrast with available data in the literature showing that cyto-c is present in the cytosol of both control and apoptosis-induced cultured cell lines. (C) 2002 Elsevier Science (USA). All rights reserved.