Inhibitory effects of Bcl-2 on mitochondrial respiration.
In contrast to the well-established anti-apoptotic effect of Bcl-2 protein, we have recently demonstrated that Bcl-2 overexpression by vaccinia virus causes apoptosis in BSC-40 cells, while it prevents apoptosis in HeLa G cells. Given the key role of mitochondria in the process of apoptosis, we focused on effects of Bcl-2 expression on mitochondrial energetics of these two cell lines. In this study we present data indicating that BSC-40 cells derive their ATP mainly from oxidative phosphorylation whereas HeLa G cells from glycolysis. More importantly, we show that in both cell lines, Bcl-2 inhibits mitochondrial respiration and causes a decrease of the ATP/ADP ratio. However, it appears that BSC-40 cells cannot sustain this decrease and die, while HeLa G cells survive, being adapted to the low ratio of ATP/ADP maintained by glycolysis. Based on this observation, we propose that the outcome of Bcl-2 expression is determined by the type of cellular ATP synthesis, namely that Bcl-2 causes apoptosis in cells relying on oxidative phosphorylation.
Vrbacký
M
M
Department of Immunology and Microbiology, First Faculty of Medicine of Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic.
Krijt
J
J
Drahota
Z
Z
Mĕlková
Z
Z
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002461:Cell Line, Transformed; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology*; D004072:Digitonin / Q000494:pharmacology; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012402:Rotenone / Q000494:pharmacology; D019802:Succinic Acid / Q000494:pharmacology; D014162:Transfection
D009840:Oligomycins; D019253:Proto-Oncogene Proteins c-bcl-2; D012402:Rotenone; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D004072:Digitonin