Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
Biochemistry (Mosc). 2020 Dec;85(12):1484-1498. doi: 10.1134/S0006297920120020.
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.
1999 年，V.P.斯库拉切夫提出了“mitoptosis”一词，用于指活细胞中线粒体的程序性消除。根据最初的想法，mitoptosis 旨在保护细胞免受受损线粒体功能障碍的影响。同时，在与氧化应激相关的大量线粒体损伤的条件下，发现了一种完整的线粒体消除的新机制。在这个实验模型中，核周区域中线粒体簇的形成导致形成“mitoptotic body”，其被单层膜包围，随后线粒体从细胞中释放。后来发现，mitoptosis 在各种正常和病理过程中发挥重要作用，这些过程不一定与线粒体损伤有关。发现 mitoptosis 发生在细胞分化、造血干细胞的自我维持、代谢重塑以及具有母系线粒体 DNA 遗传的生物中线粒体的父系线粒体的消除过程中。此外，与 mitoptosis 相关的线粒体成分释放到血液中可能参与细胞间信号的传递，也导致炎症和自身免疫性疾病的发展。Mitoptosis 可归因于酵母和一些动物细胞分裂中线粒体的不对称遗传，当有缺陷的线粒体转移到新形成的细胞之一时，就会发生这种情况。最后，在哺乳动物的整个卵泡卵巢细胞中，似乎出现了一种特定形式的 mitoptosis，即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 拷贝数显著减少。分裂后，接收主要携带有害 mtDNA 突变的线粒体的细胞死亡，从而降低了这些突变传递给后代的可能性。在正常和病理条件下研究 mitoptosis 的机制对于理解发育和衰老过程以及设计炎症、神经退行性等疾病的治疗方法都很重要。
