Abstract

In 1999 V. P. Skulachev proposed the term “mitoptosis” to refer to the programmed elimination of mitochondria in living cells. According to the initial thought, mitoptosis serves to protect cells from malfunctioning of the damaged mitochondria. At the same time, a new mechanism of the complete mitochondria elimination was found under the conditions of massive mitochondrial damage associated with oxidative stress. In this experimental model, mitochondrial cluster formation in the perinuclear region leads to the formation of “mitoptotic body” surrounded by a single-layer membrane and subsequent release of mitochondria from the cell. Later, it was found that mitoptosis plays an important role in various normal and pathological processes that are not necessarily associated with the mitochondrial damage. It was found that mitoptosis takes place during cell differentiation, self-maintenance of hematopoietic stem cells, metabolic remodelling, and elimination of the paternal mitochondria in organisms with the maternal inheritance of the mitochondrial DNA. Moreover, the associated with mitoptosis release of mitochondrial components into the blood may be involved in the transmission of signals between cells, but also leads to the development of inflammatory and autoimmune diseases. Mitoptosis can be attributed to the asymmetric inheritance of mitochondria in the division of yeast and some animal cells, when the defective mitochondria are transferred to one of the newly formed cells. Finally, a specific form of mitoptosis appears to be selective elimination of mitochondria with deleterious mutations in whole follicular ovarian cells in mammals. During formation of the primary follicle, the mitochondrial DNA copy number is significantly reduced. After division, the cells that receive predominantly mitochondria with deleterious mutations in their mtDNA die, thereby reducing the likelihood of transmission of these mutations to offspring. Further study of the mechanisms of mitoptosis in normal and pathological conditions is important both for understanding the processes of development and aging, and for designing therapeutic approaches for inflammatory, neurodegenerative and other diseases.

中文翻译：

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二十年后的骨质疏松症

摘要

VP Skulachev在1999年提出了“有丝分裂”一词，指的是在活细胞中以编程方式消除线粒体。根据最初的想法，有丝分裂作用可以保护细胞免受受损的线粒体功能障碍。同时，在与氧化应激相关的大量线粒体损伤的条件下，发现了一种完全消除线粒体的新机制。在该实验模型中，核周区域中线粒体簇的形成导致被单层膜包围的“线粒体”的形成，随后线粒体从细胞中释放出来。后来发现，细胞凋亡在各种正常和病理过程中起着重要作用，这些过程不一定与线粒体损伤有关。发现在具有母体遗传线粒体DNA的生物体中，细胞分化发生在造血干细胞的自我维持，造血干细胞的代谢重塑和父系线粒体的消除过程中。而且，与线粒体成分的凋亡发生相关的线粒体释放到血液中可能参与细胞之间的信号传递，但也导致炎性和自身免疫性疾病的发展。当缺陷的线粒体转移到新形成的细胞之一中时，线粒体可归因于线粒体在酵母和一些动物细胞分裂中的不对称遗传。最后，有丝分裂的一种特定形式似乎是在哺乳动物的完整卵泡卵巢细胞中选择性消除具有有害突变的线粒体。在初级卵泡形成过程中，线粒体DNA拷贝数明显减少。分裂后，主要接受线粒体的线粒体中具有有害突变的细胞死亡，从而降低了将这些突变传递给后代的可能性。进一步研究正常和病理条件下的细胞凋亡机制对于理解发育和衰老过程以及设计用于炎症，神经退行性疾病和其他疾病的治疗方法都是重要的。