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Mimitin – a novel cytokine-regulated mitochondrial protein

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 mitochon...

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Autores principales: Wegrzyn, Paulina, Yarwood, Stephen J, Fiegler, Nathalie, Bzowska, Monika, Koj, Aleksander, Mizgalska, Danuta, Malicki, Stanisław, Pajak, Magdalena, Kasza, Aneta, Kachamakova-Trojanowska, Neli, Bereta, Joanna, Jura, Jacek, Jura, Jolanta
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667391/
https://www.ncbi.nlm.nih.gov/pubmed/19331698
http://dx.doi.org/10.1186/1471-2121-10-23
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author Wegrzyn, Paulina
Yarwood, Stephen J
Fiegler, Nathalie
Bzowska, Monika
Koj, Aleksander
Mizgalska, Danuta
Malicki, Stanisław
Pajak, Magdalena
Kasza, Aneta
Kachamakova-Trojanowska, Neli
Bereta, Joanna
Jura, Jacek
Jura, Jolanta
author_facet Wegrzyn, Paulina
Yarwood, Stephen J
Fiegler, Nathalie
Bzowska, Monika
Koj, Aleksander
Mizgalska, Danuta
Malicki, Stanisław
Pajak, Magdalena
Kasza, Aneta
Kachamakova-Trojanowska, Neli
Bereta, Joanna
Jura, Jacek
Jura, Jolanta
author_sort Wegrzyn, Paulina
collection PubMed
description 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.
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spelling pubmed-26673912009-04-10 Mimitin – a novel cytokine-regulated mitochondrial protein Wegrzyn, Paulina Yarwood, Stephen J Fiegler, Nathalie Bzowska, Monika Koj, Aleksander Mizgalska, Danuta Malicki, Stanisław Pajak, Magdalena Kasza, Aneta Kachamakova-Trojanowska, Neli Bereta, Joanna Jura, Jacek Jura, Jolanta BMC Cell Biol Research Article 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. BioMed Central 2009-03-31 /pmc/articles/PMC2667391/ /pubmed/19331698 http://dx.doi.org/10.1186/1471-2121-10-23 Text en Copyright © 2009 Wegrzyn et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wegrzyn, Paulina
Yarwood, Stephen J
Fiegler, Nathalie
Bzowska, Monika
Koj, Aleksander
Mizgalska, Danuta
Malicki, Stanisław
Pajak, Magdalena
Kasza, Aneta
Kachamakova-Trojanowska, Neli
Bereta, Joanna
Jura, Jacek
Jura, Jolanta
Mimitin – a novel cytokine-regulated mitochondrial protein
title Mimitin – a novel cytokine-regulated mitochondrial protein
title_full Mimitin – a novel cytokine-regulated mitochondrial protein
title_fullStr Mimitin – a novel cytokine-regulated mitochondrial protein
title_full_unstemmed Mimitin – a novel cytokine-regulated mitochondrial protein
title_short Mimitin – a novel cytokine-regulated mitochondrial protein
title_sort mimitin – a novel cytokine-regulated mitochondrial protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667391/
https://www.ncbi.nlm.nih.gov/pubmed/19331698
http://dx.doi.org/10.1186/1471-2121-10-23
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