Lemeshko Victor V.
Escuela de Fisica, Facultad de Ciencias, Universidad Nacional de Colombia, sede Medellin, Calle 59-A, No 63-20, Medellin, Colombia;
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Apoptosis is defined as programmed cell death, and mitochondria, particularly their cytochrome c, play a crucial role in this process. Earlier, we discovered two populations of rat liver mitochondria with significantly different outer membrane integrity. During growth and development of the organism, the population of mitochondria with the fragile outer membrane replaced the other mitochondrial population with significantly more resistant outer membrane [Lemeshko, Biofizika, 1982, 37:837-840]. These results allowed us to suggest that the animal aging might be genetically programmed at the level of the outer membrane of mitochondria, through replacing of one population of mitochondria by the other, although both types of these organelles synthesize ATP well, as it was demonstrated in other our works. It means that the outer membrane permeabilization by the same internal and/or external environmental pro-apoptotic factors might be more probable in aged than in young organisms. The fundamental role of mitochondria in cell death has been finally recognized in 1998 [Susin et al., Mitochondria as regulator of apoptosis: doubt no more. Biochim Biophys Acta, 1998, 1366:151-165]. The “young” population of mitochondria, having the resistant outer membrane, seems to be needed to resist relatively high intensity of the free radical lipid peroxidation of biomembranes in young animals that we considered as important physiological factor allowing fast remodeling of biomembranes in young animals, allowing their growth and development. Although oxidative stress and reactive oxygen substances are widely recognized as pro-aging factors, our results clearly demonstrated that the cell antioxidant enzyme system has a low activity in young animals and significantly increases with age of rats up to half of the lifespan, thus leading to a decrease of free radical processes at this age period. Some subsequent decrease in the activity of the antioxidant enzyme system in aged animals, accompanied with relatively low rate of the membrane structure recovery, might be the fundamental basis for the development of degenerative diseases and even death events, as a result of increased population of “aged” mitochondria having fragile outer membrane. All these mean that not directly the death, but the probability of its realization under external environmental conditions is genetically programmed. A somewhat similar situation takes place at the cellular level that relates to the cytochrome c-mediated cell death. The release of cytochrome c from mitochondria under various pro-apoptotic factors, for example, does not yet mean cell death: as long as cytoplasmic reducing factors maintain cytochrome c in the reduced state, this hemoprotein is not yet pro-apoptotic. We recently demonstrated that only oxidized, but not reduced form of cytochrome c is capable to directly induce mitochondrial aggregation [Lemeshko, Mol.Cell. Biochem., 2012, 360:111-119], the process known as one of the attributes of apoptosis. In conclusion, we hypothesize that the probability of death of multicellular organisms is significantly contributed by genetically programmed structural and functional changes of various cells, like a change in mitochondrial populations, which increase the probability of multiple apoptotic processes.