Open AccessApoptotic Cell Death Induced by Inhibitors of Energy Conservation
Author(s) -
Marton Attila,
Mihalik Rudolf,
Bratincsák András,
Adleff Vilmos,
Peták István,
Végh Miklós,
Bauer Pál I.,
Krajcsi Péter
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.0467a.x
Subject(s) - apoptosis , microbiology and biotechnology , glycolysis , programmed cell death , oxidative phosphorylation , citric acid cycle , fragmentation (computing) , dna fragmentation , mitochondrion , biology , chemistry , intrinsic apoptosis , biochemistry , caspase , metabolism , ecology
Energy charge controls intermediary metabolism and cellular regulation. Here we show that inhibition of energy conservation at the level of glucose uptake, glycolysis, citric acid cycle, and oxidative phosphorylation induces cell death, leading to fragmentation of DNA into an oligonucleosomal ladder and morphological changes typical for apoptosis. Bc1‐2, the prototype of oncogenes that suppress cell death, efficiently inhibits apoptosis induced by metabolic inhibitors. Bcl‐2 does not antagonize the inhibitory potential of mitochondrial inhibitors, and cannot prevent or delay the decrease of the cellular ATP level subsequent to metabolic inhibition. Thus, we propose that Bcl‐2 blocks apoptosis at a point downstream of the collapse of the cellular‐energy homeostasis.