Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): Formation of mitoptotic bodies and extrusion of mitochondrial material from the cell

Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): Formation of mitoptotic bodies and extrusion of mitochondrial material from the cell
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DOI:
10.1016/j.bbabio.2008.03.027
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发表时间:
2008-07-01
影响因子:
4.3
通讯作者:
Skulachev, Vladimir P.
Skulachev, Vladimir P.
中科院分区:
生物学2区
文献类型:
--
作者:
Lyamzaev, Konstantin G.;Nepryakhina, Olga K.;Skulachev, Vladimir P.

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当线粒体水解糖酵解 ATP 而不是产生呼吸 ATP 时,能量灾难已被模拟。在高度糖酵解的 HeLa 细胞中,呼吸抑制和氧化磷酸化解偶联 2-4 天后,30-50% 的细胞群存活。存活伴随着线粒体的选择性消除。这种类型的有丝分裂包括(i)线粒体丝的裂变,(ii)在核周区域中所产生的圆形线粒体的聚集,(iii)线粒体簇被膜封闭(形成“有丝分裂体”),(iv)该体内的线粒体分解成小膜囊泡,(v)体从细胞中突出,以及(vi)体边界膜的破坏。自噬不参与该有丝分裂程序。增加活性氧 (ROS) 的产生对于执行该程序是必要的,因为抗氧化剂可以防止有丝分裂并杀死用线粒体毒物处理的细胞,就好像 ROS 相关的有丝分裂在严重线粒体应激条件下可以保护细胞一样。提示有丝分裂小体的胞吐作用可能参与网织红细胞和晶状体纤维细胞的成熟。 (c) 2008 Elsevier B.V. 保留所有权利。
Energy catastrophe, when mitochondria hydrolyze glycolytic ATP instead of producing respiratory ATP, has been modeled. In highly glycolyzing HeLa cells, 30-50% of the population survived after inhibition of respiration and uncoupling of oxidative phosphorylation for 2-4 days. The survival was accompanied by selective elimination of mitochondria. This type of mitoptosis includes (i) fission of mitochondrial filaments, (ii) clustering of the resulting roundish mitochonclFia in the perinuclear area, (iii) occlusion of mitochondrial clusters by a membrane (formation of a "mitoptotic body"), (iv) decomposition of mitochondfia inside this body to small membrane vesicles, (v) protrusion of the body from the cell, and (vi) disruption of the body boundary membrane. Autophagy was not involved in this mitoptotic program. Increased production of reactive oxygen species (ROS) was necessary for execution of the program, since antioxiclants prevent mitoptosis and kill the cells treated with the mitochondrial poisons as if a ROS-linked mitoptosis serves for protection of the cells under conditions of severe mitochonclFial stress. It is suggested that exocytosis of mitoptotic bodies may be involved in maturation of reticulocytes and lens fiber cells. (c) 2008 Elsevier B.V. All rights reserved.