Skulachev Vladimir P, Bakeeva Lora E, Chernyak Boris V, Domnina Lidia V, Minin Alexander A, Pletjushkina Olga Yu, Saprunova Valeria B, Skulachev Innokenty V, Tsyplenkova Valeria G, Vasiliev Jury M, Yaguzhinsky Lev S, Zorov Dmitry B
Department of Bioenergetics and Mathematical Methods in Biology, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):341-58. doi: 10.1023/b:mcbi.0000009880.94044.49.
Association of mitochondrial population to a mitochondrial reticulum is typical of many types of the healthy cells. This allows the cell to organize a united intracellular power-transmitting system. However, such an association can create some difficulties for the cell when a part of the reticulum is damaged or when mitochondria should migrate from one cell region to another. It is shown that in these cases decomposition of extended mitochondria to small roundish organelles takes place (the thread-grain transition). As an intermediate step of this process, formation of beads-like mitochondria occurs when several swollen parts of the mitochondrial filament are interconnected with thin thread-like mitochondrial structures. A hypothesis is put forward that the thread-grain transition is used as a mechanism to isolate a damaged part of the mitochondrial system from its intact parts. If the injury is not repaired, spherical mitochondrion originated from the damaged part of the reticulum is assumed to convert to a small ultracondensed and presumably dead mitochondrion (this process is called 'mitoptosis'). Then the dead mitochondrion is engulfed by an autophagosome. Sometimes, an ultracondensed mitoplast co-exists with a normal mitoplast, both of them being surrounded by a common outer mitochondrial membrane. During apoptosis, massive thread-grain transition is observed which, according to Youle et al. (S. Frank et al., Dev Cell 1: 515, 2002), is mediated by a dynamin-related protein and represents an obligatory step of the mitochondria-mediated apoptosis. We found that there is a lag phase between addition of an apoptogenic agent and the thread-grain transition. When started, the transition occurs very fast. It is also found that this event precedes complete de-energization of mitochondria and cytochrome c release to cytosol. When formed, small mitochondria migrate to (and in certain rare cases even into) the nucleus. It is suggested that small mitochondria may serve as a transportable form of organelles ('cargo boats' transporting some apoptotic proteins to their nuclear targets).
线粒体群体与线粒体网状结构的关联是许多类型健康细胞的典型特征。这使细胞能够构建一个统一的细胞内能量传输系统。然而，当网状结构的一部分受损或线粒体需要从细胞的一个区域迁移到另一个区域时，这种关联可能会给细胞带来一些困难。研究表明，在这些情况下，会发生延长的线粒体分解为小圆形细胞器的过程（丝状-颗粒状转变）。作为这一过程的中间步骤，当线粒体细丝的几个肿胀部分通过细的丝状线粒体结构相互连接时，会形成珠状线粒体。有人提出一个假说，即丝状-颗粒状转变被用作一种机制，将线粒体系统的受损部分与其完整部分隔离开来。如果损伤没有得到修复，源自网状结构受损部分的球形线粒体被认为会转变为一个小的超浓缩且可能死亡的线粒体（这个过程称为“线粒体凋亡”）。然后，死亡的线粒体被自噬体吞噬。有时，一个超浓缩的线粒体小体与一个正常的线粒体小体共存，它们都被共同的线粒体外膜包围。在细胞凋亡过程中，会观察到大量的丝状-颗粒状转变，根据尤勒等人（S. 弗兰克等人，《发育细胞》1: 515, 2002）的研究，这是由一种与发动蛋白相关的蛋白质介导的，并且是线粒体介导的细胞凋亡的一个必要步骤。我们发现，在添加凋亡诱导剂与丝状-颗粒状转变之间存在一个延迟期。一旦开始，转变发生得非常快。还发现这个事件先于线粒体的完全去能化和细胞色素c释放到细胞质中。当形成时，小线粒体迁移到细胞核（在某些罕见情况下甚至进入细胞核）。有人提出，小线粒体可能作为细胞器的一种可运输形式（“货船”将一些凋亡蛋白运输到它们的核靶点）。
