Activation of murine-derived J774.A1 macrophages with interferon γ and lipopolysaccharide leads to a progressive mitochondrial defect characterized by inhibition of oxygen consumption and a decrease in the generation of ATP by oxidative phosphorylation. These changes are dependent on the generation of nitric oxide (NO) by an inducible NO synthase that becomes a significant consumer of oxygen. Furthermore, in these activated cells there is a biphasic stabilization of the hypoxia-inducible factor HIF1α, the second phase of which is also dependent on the presence of NO. The mitochondrial defect and stabilization of HIF1α synergize to activate glycolysis, which, at its maximum, generates quantities of ATP greater than those produced by non-activated cells. Nevertheless, the amount of ATP generated is not sufficient to fulfil the energy requirements of the activated cells, probably leading to a progressive energy deficit with the consequent inhibition of cell proliferation and death.
Retraction of: J. Cell Sci. 121, 3468-3475.
The authors wish to retract the above paper. We have recently identified errors affecting certain figure panels in Fig. 5 in which control data were processed inappropriately such that the figure panels do not accurately report the original data. The misuse and re-use of western blot bands violates the editorial policy of Journal of Cell Science, and so we must retract this article. A. G. regrets the inappropriate figure manipulations, of which his co-author was completely unaware.
We sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of these data.
We are grateful to Catia Andreassi and Annie Higgs for reading the manuscript and for their very useful comments and suggestions. We also thank Leanne Boorn for valuable assistance in some of the experiments.
- Accepted July 8, 2008.
- © The Company of Biologists Limited 2008