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Open Access Research article

Xanthurenic acid translocates proapoptotic Bcl-2 family proteins into mitochondria and impairs mitochondrial function

Halina Z Malina1* and Otto M Hess2

Author Affiliations

1 Xanthurenic Acid Laboratory, Department Cardiology, Inselspital, CH-3010 Bern, Switzerland

2 Swiss Cardiovascular Research Center, University Hospital-Inselspital, CH-3010 Bern, Switzerland

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BMC Cell Biology 2004, 5:14  doi:10.1186/1471-2121-5-14

Published: 6 April 2004

Abstract

Background

Xanthurenic acid is an endogenous molecule produced by tryptophan degradation, produced in the cytoplasm and mitochondria. Its accumulation can be observed in aging-related diseases, e.g. senile cataract and infectious disease. We previously reported that xanthurenic acid provokes apoptosis, and now present a study of the response of mitochondria to xanthurenic acid.

Results

Xanthurenic acid at 10 or 20 μM in culture media of human aortic smooth muscle cells induces translocation of the proteins Bax, Bak, Bclxs, and Bad into mitochondria. In 20 μM xanthurenic acid, Bax is also translocated to the nucleus. In isolated mitochondria xanthurenic acid leads to Bax and Bclxs oligomerization, accumulation of Ca2+, and increased oxygen consumption.

Conclusion

Xanthurenic acid interacts directly with Bcl-2 family proteins, inducing mitochondrial pathways of apoptosis and impairing mitochondrial functions.

Keywords:
xanthurenic acid; human aortic smooth muscle cells; Bax; Bak; Bcl-xs; Bad; translocation; mitochondria; O2 consumption; Ca2+