Mimitin - a novel cytokine-regulated mitochondrial protein

Paulina Wegrzyn, Stephen J Yarwood, Nathalie Fiegler, Monika Bzowska, Aleksander Koj, Danuta Mizgalska, Stanisław Malicki, Magdalena Pajak, Aneta Kasza, Neli Kachamakova-Trojanowska, Joanna Bereta, Jacek Jura, Jolanta Jura

    Research output: Contribution to journalArticle

    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.

    Original languageEnglish
    Article number23
    JournalBMC Cell Biology
    Volume10
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Apoptosis
    • Caspase 3
    • Caspase 7
    • Cell Line, Tumor
    • Humans
    • Interleukin-1
    • Interleukin-6
    • MAP Kinase Signaling System
    • Microtubule-Associated Proteins
    • Mitochondrial Proteins
    • Molecular Chaperones
    • RNA, Small Interfering
    • Signal Transduction
    • Time Factors
    • Two-Hybrid System Techniques
    • Up-Regulation

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  • Cite this

    Wegrzyn, P., Yarwood, S. J., Fiegler, N., Bzowska, M., Koj, A., Mizgalska, D., Malicki, S., Pajak, M., Kasza, A., Kachamakova-Trojanowska, N., Bereta, J., Jura, J., & Jura, J. (2009). Mimitin - a novel cytokine-regulated mitochondrial protein. BMC Cell Biology , 10, [23]. https://doi.org/10.1186/1471-2121-10-23