Inhibitors of Mitochondrial Energy Production Prevent DNA Internucleosomal Fragmentation in Thymocytes

V. E. Galitovsky and V. G. Gogvadze^*

Institute of Theoretical and Experimental Biophysics, Pushchino, Moscow Region, 142292 Russia; fax: (096) 779-0553; E-mail: gogvadze@venus.iteb.serpukhov.su

^* To whom correspondence should be addressed.

Received August 13, 1997; Revision received June 18, 1998

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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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KEY WORDS: apoptosis, mitochondria, calcium

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