title: Apoptotic cell death induced by inhibitors of energy conservation--Bcl-2 inhibits apoptosis downstream of a fall of ATP level.
abstract: 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. Bcl-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.
authors.affiliation: Department of Medical Biochemistry, Semmelweis University of Medicine, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Marton
authors.forename: R
authors.initials: R
authors.lastname: Mihalik
authors.forename: A
authors.initials: A
authors.lastname: Bratincsák
authors.forename: V
authors.initials: V
authors.lastname: Adleff
authors.forename: I
authors.initials: I
authors.lastname: Peták
authors.forename: M
authors.initials: M
authors.lastname: Végh
authors.forename: P I
authors.initials: PI
authors.lastname: Bauer
authors.forename: P
authors.initials: P
authors.lastname: Krajcsi
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004579:Electron Transport; D004734:Energy Metabolism; D006019:Glycolysis; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D000255:Adenosine Triphosphate