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Galitovsky VE, Gogvadze VG: Inhibitors of mitochondrial energy production prevent DNA internucleosomal fragmentation in thymocytes. Biochemistry. 1998 Dec;63(12):1374-7. Apoptosis or programmed cell death is a gene-controlled process of cell self-destruction. One of the earliest manifestations of apoptosis, which precedes morphological changes, is a decrease of mitochondrial membrane potential. Here we show that neither inhibitors of the mitochondrial respiratory chain (rotenone and antimycin) nor an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), agents which decrease the mitochondrial membrane potential, induce DNA internucleosomal fragmentation, but all of them markedly prevent fragmentation induced either by glucocorticoids or the Ca2+ ionophore A23187. A similar effect was also observed in the presence of a mitochondrial ATPase inhibitor (oligomycin). The inhibition of DNA internucleosomal fragmentation can be explained by the ability of inhibitors to prevent the mitochondrial permeability transition--a key event in apoptosis induction. |
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