Thread-grain transition of mitochondrial reticulum as a step of mitoptosis and apoptosis

• Published in: Molecular and cellular biochemistry Vol. 256-257; no. 1-2; pp. 341 - 358
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.01.2004
• Subjects: Animals; Apoptosis; Boats; Cytochromes c - metabolism; Humans; Mitochondria; Mitochondria - enzymology; Mitochondria - physiology; Mitochondria - ultrastructure; Proteins; Reactive Oxygen Species; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0300-8177; 1573-4919
• 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).