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Mimitin - a novel cytokine-regulated mitochondrial protein.
Wegrzyn, Paulina; Yarwood, Stephen J; Fiegler, Nathalie; Bzowska, Monika; Koj, Aleksander; Mizgalska, Danuta; Malicki, Stanislaw; Pajak, Magdalena; Kasza, Aneta; Kachamakova-Trojanowska, Neli; Bereta, Joanna; Jura, Jacek; Jura, Jolanta.
Afiliação
  • Wegrzyn P; Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. p.wegrzyn@uj.edu.pl
BMC Cell Biol ; 10: 23, 2009 Mar 31.
Article em En | MEDLINE | ID: mdl-19331698
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-6 / Interleucina-1 / Chaperonas Moleculares / Proteínas Mitocondriais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: BMC Cell Biol Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Polônia País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-6 / Interleucina-1 / Chaperonas Moleculares / Proteínas Mitocondriais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: BMC Cell Biol Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Polônia País de publicação: Reino Unido