Mimitin - a novel cytokine-regulated mitochondrial protein

Wegrzyn, P. et al. (2009) Mimitin - a novel cytokine-regulated mitochondrial protein. BMC Cell Biology, 10(23), (doi: 10.1186/1471-2121-10-23)

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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Yarwood, Dr Stephen
• Authors: Wegrzyn, P., Yarwood, S.J., Fiegler, N., Bzowska, M., Koj, A., Mizgalska, D., Malicki, S., Pajak, M., Kasza, A., Kachamakova-Trojanowska, N., Bereta, J., and Jura, J.
• Subjects: Q Science > QR Microbiology > QR180 Immunology; Q Science > QH Natural history > QH301 Biology
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: BMC Cell Biology
• Publisher: Biomed Central
• ISSN: 1471-2121