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Open Access Research article

Mimitin – a novel cytokine-regulated mitochondrial protein

Paulina Wegrzyn1, Stephen J Yarwood2, Nathalie Fiegler1, Monika Bzowska1, Aleksander Koj1, Danuta Mizgalska1, Stanisław Malicki1, Magdalena Pajak1, Aneta Kasza1, Neli Kachamakova-Trojanowska1, Joanna Bereta1, Jacek Jura3 and Jolanta Jura1*

Author Affiliations

1 Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland

2 Faculty of Biomedical and Life Sciences, University of Glasgow, UK

3 National Research Institute of Animal Production, Department of Biotechnology of Animal Reproduction, Balice, Poland

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BMC Cell Biology 2009, 10:23  doi:10.1186/1471-2121-10-23

Published: 31 March 2009

Abstract

Background

The product of a novel cytokine-responsive gene discovered by differential display analysis in our earlier studies on HepG2 cells was identified as mimitin – a small mitochondrial protein. Since proinflammatory cytokines are known to affect components of the respiratory chain in mitochondria, and mimitin was reported as a possible chaperone for assembly of mitochondrial complex I, we looked for the effects of modulation of mimitin expression and for mimitin-binding partners.

Results

By blocking mimitin expression in HepG2 cells by siRNA we found that mimitin has no direct influence on caspase 3/7 activities implicated in apoptosis. However, when apoptosis was induced by TNF and cycloheximide, and mimitin expression blocked, the activities of these caspases were significantly increased. This was accompanied by a slight decrease in proliferation of HepG2 cells. Our observations suggest that mimitin may be involved in the control of apoptosis indirectly, through another protein, or proteins. Using the yeast two-hybrid system and coimmunoprecipitation we found MAP1S among proteins interacting with mimitin. MAP1S is a recently identified member of the microtubule-associated protein family and has been shown to interact with NADH dehydrogenase I and cytochrome oxidase I. Moreover, it was implicated in the process of mitochondrial aggregation and nuclear genome destruction. The expression of mimitin is stimulated more than 1.6-fold by IL-1 and by IL-6, with the maximum level of mimitin observed after 18–24 h exposure to these cytokines. We also found that the cytokine-induced signal leading to stimulation of mimitin synthesis utilizes the MAP kinase pathway.

Conclusion

Mimitin is a mitochondrial protein upregulated by proinflammatory cytokines at the transcriptional and protein levels, with MAP kinases involved in IL-1-dependent induction. Mimitin interacts with a microtubular protein (MAP1S), and some changes of mimitin gene expression modulate activity of apoptotic caspases 3/7, suggesting that this protein may indirectly participate in apoptosis.