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Inhibitory Effects of Bcl-2 on
Mitochondrial Respiration
M. VRBACKÝ1,2, J.
KRIJT3, Z. DRAHOTA4, Z. MĚLKOVÁ1,2
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
Summary
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:
zmelk@LF1.cuni.cz
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