Physiol. Res. 52: 545-554, 2003

Inhibitory Effects of Bcl-2 on Mitochondrial Respiration


1Institute of Pathological Physiology, 2Department of Immunology and Microbiology, 3Department of the Inherited Metabolic Diseases, First Faculty of Medicine, Charles University, Prague, and 4Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Received July 12, 2002
Accepted November 5, 2002

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.

Key words
Bcl-2 • Apoptosis • ATP • Mitochondrial respiration

Reprint requests
Zora Mělková, M.D., Ph.D., Department of Immunology and Microbiology, First Faculty of Medicine of Charles University, Studničkova 7, 128 00 Prague 2, Czech Republic, e-mail:

© 2003 by the Institute of Physiology, Czech Academy of Sciences