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FEBS Lett. 1996 Nov 11;397(1):7-10.

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

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1
Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russian Federation. skulach@head.genebee.msu.su.

Abstract

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).

PMID:
8941703
[Indexed for MEDLINE]
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