| Autor: |
Kachamakova-Trojanowska Neli, Kasza Aneta, Pajak Magdalena, Malicki Stanisław, Mizgalska Danuta, Koj Aleksander, Bzowska Monika, Fiegler Nathalie, Yarwood Stephen J, Wegrzyn Paulina, Bereta Joanna, Jura Jacek, Jura Jolanta |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
BMC Cell Biology, Vol 10, Iss 1, p 23 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2121 |
| DOI: |
10.1186/1471-2121-10-23 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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