Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): formation of mitoptotic bodies and extrusion of mitochondrial material from the cell.
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 mitochondria in the perinuclear area, (iii) occlusion of mitochondrial clusters by a membrane (formation of a "mitoptotic body"), (iv) decomposition of mitochondria 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 antioxidants 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 mitochondrial stress. It is suggested that exocytosis of mitoptotic bodies may be involved in maturation of reticulocytes and lens fiber cells.
Lyamzaev
Konstantin G
KG
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University Moscow 119992, Russia.
Nepryakhina
Olga K
OK
Saprunova
Valeria B
VB
Bakeeva
Lora E
LE
Pletjushkina
Olga Yu
OY
Chernyak
Boris V
BV
Skulachev
Vladimir P
VP
D017209:Apoptosis; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival; D003600:Cytosol / Q000502:physiology; D004734:Energy Metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species