Two critical factors affecting the release of mitochondrial cytochrome c as revealed by studies using N,N′-dicyclohexylcarbodiimide as an atypical inducer of permeability transition
Two critical factors affecting the release of mitochondrial cytochrome c as revealed by studies using N,N′-dicyclohexylcarbodiimide as an atypical inducer of permeability transition
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DOI：
10.1007/s10863-005-8641-6
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发表时间：
2005-10-01
影响因子：
3
通讯作者：
Shinohara, Y
中科院分区：
文献类型：
--
作者：
Yamamoto, T;Terauchi, S;Shinohara, Y
早期报道称，N,N'-二环己基碳二亚胺 (DCCD) 添加到线粒体悬浮液中时，对线粒体呼吸具有刺激作用并诱导线粒体肿胀。这些数据似乎暗示 DCCD 引起线粒体通透性转变 (PT)，但这种可能性从未被研究过。本研究详细研究了DCCD对线粒体结构和功能的影响。发现 DCCD 以环孢素 A 不敏感的方式诱导线粒体 PT。电子显微镜分析也支持 DCCD 诱导线粒体 PT。然而，与许多其他 PT 诱导剂不同，DCCD 未能引起线粒体细胞色素 c 的大量释放。为了了解线粒体 PT 的诱导与线粒体细胞色素 c 释放之间的关系，我们将 DCCD 对线粒体结构和功能的作用与 Ca2+（称为普通 PT 诱导剂）的作用进行了比较。因此，线粒体体积和线粒体耗氧速度被认为是控制 PT 诱导过程中线粒体细胞色素 c 释放的关键参数。
N,N'-dicyclohexylcarbodiimide (DCCD) was earlier reported to have stimulatory effects on mitochondrial respiration and to induce mitochondrial swelling, when it was added to mitochondrial suspensions. These data seem to imply that DCCD caused the mitochondrial permeability transition (PT), but this possibility had never been investigated. In the present study, effects of DCCD on the mitochondrial structure and function were studied in detail. DCCD was found to induce mitochondrial PT in a cyclosporine A-insensitive manner. Electron microscopic analysis also supported the induction of the mitochondrial PT by DCCD. However, different from many other PT inducers, DCCD failed to cause massive release of mitochondrial cytochrome c. To understand the relationship between the induction of mitochondrial PT and the release of mitochondrial cytochrome c, we compared the actions of DCCD on mitochondrial structure and function with those of Ca2+, known as an ordinary PT inducer. As a result, two parameters considered to be critical for controlling the release of mitochondrial cytochrome c on the induction of PT were mitochondrial volume and the velocity of mitochondrial oxygen consumption.