Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide‐producing mitochondria and cell

FEBS Letters

Skulachev, Vladimir P.¹ 

[1] Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russian Federation

关键词: Mitochondria;    Apoptosis;    Permeability transition pore;    Reactive oxygen species;    HIV;    ROS;    reactive oxygen species;    TNP;    tumor necrosis factor;    z-VAD.fmk;    N-benzylcarbonyl-Val-Ala-Asp-fluoromethylketone;   

DOI  :  10.1016/0014-5793(96)00989-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Petit and co-authors have recently summarized results of their studies on the involvement of mitochondria in apoptosis [Petit et al. (1996) FEBS Lett. 396, 7–13]. The mechanism consists in the release to the cytosol of a protein (presumably a protease) that is normally sequestered in the intermembrane space of mitochondria. This protein, when added to isolated nuclei, caused typical apoptotic changes. Its release from mitochondria was shown to occur as a result of disruption of the outer mitochondrial membrane due to swelling of mitochondria caused by opening of so-called permeability transition pores in their inner membranes. Increase in the level of products of the one-electron reduction of O₂ (reactive oxygen species, ROS) is known to induce the mitochondrial pores. The hypothesis described here assumes that pore formation and apoptosis are involved in the organization of a defense system preventing ROS formation. It is proposed that ROS-induced pore opening lowers ROS production due to (a) maximal stimulation of mitochondrial O₂ consumption and, hence, intracellular [O₂] lowering and (b) complete dissipation of mitochondrial membrane potentials and, as a consequence, maximal oxidation of such respiratory chain carriers as CoQ^.– which serve as one-electron O₂ reductants. ROS decrease allows pore closure. If, nevertheless, ROS are still accumulating in a mitochondrion, long-lived pores cause degradation of the organelle which cannot import and synthesize proteins due to the absence of the membrane potential. In this way, ROS-producing mitochondria can be eliminated (mitochondrial selection). Another result of the long-lived pores is mitochondrial swelling. This disrupts the outer mitochondrial membrane and releases the apoptosis-inducing protein. Apoptosis eliminates ROS-producing cells (cell selection).

【 授权许可】

Unknown