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The role of iron in the proliferation of Drosophila l(2)mbn cells
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. (Maria Lind Karlberg)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. (Maria Lind Karlberg)
2010 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 400, no 3, 442-446 p.Article in journal (Refereed) Published
Abstract [en]

Iron is essential for life and is needed for cell proliferation and cell cycle progression. Iron deprivation induces cell cycle arrest and finally apoptosis. The Drosophila tumorous larval hemocyte cell line l(2)mbn was used to study the sensitivity and cellular response to iron deprivation through the chelator desferrioxamine (DFO). At a concentration of 10 mM DFO or more the proliferation was inhibited reversibly, while the amount of dead cells did not increase. FACS analysis showed that the cell cycle was arrested in G1/S phase and the transcript level of cycE was decreased to less than 50% of control cells. These results show that iron chelation in this insect tumorous cell line causes a specific and coordinated cell cycle arrest.

Place, publisher, year, edition, pages
2010. Vol. 400, no 3, 442-446 p.
Keyword [en]
iron drosophila cell cycle arrest cyclin cell proliferation
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Comparative Physiology
Identifiers
URN: urn:nbn:se:uu:diva-114118DOI: 10.1016/j.bbrc.2010.08.100ISI: 000282616200027OAI: oai:DiVA.org:uu-114118DiVA: diva2:293033
Available from: 2010-02-10 Created: 2010-02-10 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Mitochondrial Iron Metabolism: Study of mitoferrin in Drosophila melanogaster
Open this publication in new window or tab >>Mitochondrial Iron Metabolism: Study of mitoferrin in Drosophila melanogaster
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Iron has a dualistic character. On the one hand it is essential for the life of most organisms, on the other hand it is involved in the generation of reactive oxygen species that are implicated in diseases and aging. During evolution efficient mechanisms for uptake, handling and storage of iron in a safe way have developed to keep the balance between iron availability and minimizing the hazards. In eukaryotes, mitochondria are the central organelle for “metabolizing” iron and consequently play an important role in cellular iron homeostasis.

Mitoferrins are mitochondrial carrier proteins, which are involved in iron transport into mitochondria. In vertebrates two mitoferrins exist, one (mitoferrin1) of which is essential for heme synthesis during erythropoiesis, while the function of the other (mitoferrin2) is not well defined. In the fruit fly we found only one mitoferrin gene (dmfrn), which codes most likely for a functional homologueof vertebrate mitoferrin2.

In Drosophila cell culture, dmfrn overexpression resulted in an overestimation of cell sensed iron levels. The signal responsible for this, is most likely a yet unidentified compound of ISC synthesis. In the cell culture system we also showed that iron chelation blocks the progression of the cell cycle in a reversible and therefore most likely controlled way.

Study of different dmfrn mutants indicates a role of dmfrn during spermatogenesis and development to adulthood. As dmfrn deletion mutants are not lethal, it is likely that other lower affinity iron transporters exist. A similar conclusion has been drawn by others from the study of yeast mitoferrin homologuemutants. Rim2p/Mrs12p has recently been implicated in mitochondrial iron transport, and might be an alternative metal carrier. We identified a putative homologuein the fruit fly and found a possible link between mutants in this gene and iron.

Our results emphasize the importance of the mitochondrial iron metabolism in cellular iron homeostasis. We also show for the first time, a direct connection between the mitochondrial iron metabolism and spermatogenesis. Mutants characterized and developed by us will help to study these processes in further detail and reveal the underlying mechanisms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 713
Keyword
iron, Drosophila, mitochondria, mitoferrin, ferritin, spermatogenesis, cell cycle, DFO, MRS12
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Comparative Physiology
Identifiers
urn:nbn:se:uu:diva-114201 (URN)978-91-554-7722-6 (ISBN)
Public defence
2010-03-25, Lindahlsalen, Evolutionary Biology Centre, Norbyvägen 18A, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2010-03-03 Created: 2010-02-11 Last updated: 2010-03-03Bibliographically approved

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Metzendorf, ChristophLind, Maria I

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