Unique Behavior and Function of the Mitochondrial Ribosomal Protein S4 (RPS4) in Early Dictyostelium Development

Hosoya, Koh-ichi; Amagai, Aiko; Chida, Junji; Maeda, Yasuo

doi:10.2108/zsj.20.1455

Cited by 10 publications

(10 citation statements)

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“…Therefore, the 16S mitochondrial rRNA seems to be transferred from the organelle to the nucleus of speamatogenic cells by means of an unknown mechanism of RNA translocation. This also suggests that the mitochondrial membrane may be somewhat leaky to release some intramitochondrial molecules such as rRNAs, and more importantly that some of Dictyostelium mt- rps4 mRNA and/or RPS4 protein (mt-RPS4) may be able to go out from mitochondria and ready to be transferred into the nucleus, because Dictyostelium mt-RPS4 has several nuclear-localization sequences in the molecule, as noted before [10,18]. …”

Section: Involvements Of the Mitochondrial Functions In A Variety mentioning

confidence: 65%

“…As was expected, partial disruption of mt-rps4 was found to cause impaired differentiation, thus resulting in the failure of many cells to aggregate even after a prolonged time of starvation [10]. Transformants ( rps4 AS cells) generated by antisense-mediated gene inactivation also exhibit markedly delayed differentiation; most of them showed no sign of aggregation and remained as round-shaped single cells even after 16 h of incubation [18]. In contrast, the initial step of cell differentiation including aggregation under the submerged conditions was enhanced in rps4 OE cells overexpressing the mt-rps4 mRNA in the extramitochondrial cytoplasm [10].…”

Section: Induction Of Cell Differentiation By Mitochondrial Ribosomentioning

confidence: 87%

“…Based on PSORTII prediction, when the mt-RPS4 protein is released into the cytosol, it is predicted to move preferentially to the nucleus. It was confirmed by the immunohistochemical method using the anti-mt-RPS4 antibody that the mt-RPS4 protein produced in the cytoplasm of the rps4 OE cells is capable of moving into the nucleus [18]. Again, it is worth noting that the partial disruption (mitochondrial heteroplasmy) of the rps4 gene greatly impairs differentiation, including cell aggregation.…”

Section: Induction Of Cell Differentiation By Mitochondrial Ribosomentioning

confidence: 99%

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Control of Cell Differentiation by Mitochondria, Typically Evidenced in Dictyostelium Development

Maeda

Chida

2013

Biomolecules

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In eukaryotic cells, mitochondria are self-reproducing organelles with their own DNA and they play a central role in adenosine triphosphate (ATP) synthesis by respiration. Increasing evidence indicates that mitochondria also have critical and multiple functions in the initiation of cell differentiation, cell-type determination, cell movement, and pattern formation. This has been most strikingly realized in development of the cellular slime mold Dictyostelium. For example, the expression of the mitochondrial ribosomal protein S4 (mt-rps4) gene is required for the initial differentiation. The Dictyostelium homologue (Dd-TRAP1) of TRAP-1 (tumor necrosis receptor-associated protein 1), a mitochondrial molecular chaperone belonging to the Hsp90 family, allows the prompt transition of cells from growth to differentiation through a novel prestarvation factor (PSF-3) in growth medium. Moreover, a cell-type-specific organelle named a prespore-specific vacuole (PSV) is constructed by mitochondrial transformation with the help of the Golgi complex. Mitochondria are also closely involved in a variety of cellular activities including CN-resistant respiration and apoptosis. These mitochondrial functions are reviewed in this article, with special emphasis on the regulation of Dictyostelium development.

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Section: Involvements Of the Mitochondrial Functions In A Variety mentioning

confidence: 65%

Section: Induction Of Cell Differentiation By Mitochondrial Ribosomentioning

confidence: 87%

Section: Induction Of Cell Differentiation By Mitochondrial Ribosomentioning

confidence: 99%

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Control of Cell Differentiation by Mitochondria, Typically Evidenced in Dictyostelium Development

Maeda

Chida

2013

Biomolecules

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“…Based on PSORTII prediction, mysteriously enough, the Dd-MRP4 is very unique in that it is a mitochondrial protein encoded by mt-DNA itself, but has several nuclear localization signals in the molecule [21]. Actually, it has been confirmed that the Dd-MRP4 protein produced in the cytoplasm of the Dd-mrp4 OE cells is preferentially transferred into the nucleus [35]. Although the fact that only the MRP4 protein of Dictyostelium has several nuclear localization signals is puzzling, at least a part of the Dd-MRP4 protein seems to work in the nucleus to regulate cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Specific growth suppression of human cancer cells by targeted delivery of Dictyostelium mitochondrial ribosomal protein S4

2014

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BackgroundIn general, growth and differentiation are mutually exclusive but are cooperatively regulated throughout development. Thus, the process of a cell’s switching from growth to differentiation is of great importance not only for the development of organisms but also for malignant transformation, in which this process is reversed. We have previously demonstrated using a Dictyostelium model system that the Dictyostelium mitochondrial ribosomal protein S4 (Dd-mrp4) gene expression is essential for the initiation of cell differentiation: Dd-mrp4-null cells fail to initiate differentiation, while the initial step of cell differentiation and the subsequent morphogenesis are markedly enhanced in mrp4OE cells overexpressing the Dd-mrp4 in the extramitochondrial cytoplasm. This raised a possibility that the ectopically enforced expression of the Dd-mrp4 in human cells might inhibit their growth, particularly of malignant tumor cells, by inducing cell differentiation.MethodsFour kinds of human tumor cell lines were transfected by three kind of vector constructs (the empty vector: pcDNA3.1 (Mock); pcDNA3.1-rps4 bearing Dictyostelium cytoplasmic ribosomal protein S4; pcDNA3.1-mrp4 bearing Dictyostelium mitochondrial ribosomal protein S4). As controls, four kinds of human primary cultured cells were similarly transfected by the above vector constructs. After transfection, growth kinetics of cells was analyzed using cell viability assay, and also the TUNEL method was used for evaluation of apoptotic cells.ResultsEctopically expressed Dd-mrp4 suppressed cell proliferation through inducing apoptotic cell death specifically in the human lung adenocarcinoma (A549), epithelial cervical cancer (HeLa), hepatocellular carcinoma (HepG2) and colonic carcinoma (Caco-2), but not in primary cultured normal cells, such as human brain microvascular endothelial cells (HBMECs); human umbilical vein endothelial cells (HUVECs) and human normal hepatocytes (hHeps™), with one exception (human cardiac fibloblasts (HCF)).ConclusionThe present finding that the ectopically enforced expression of Dd-mrp4 in human several tumor cell lines specifically suppresses their proliferation suggests strongly that the Dd-mrp4 gene derived from Dictyostelium mitochondria may provide a new promising therapeutic strategy for disrupting cell viability pathways in human cancers.

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“…1999). Transformants ( rps4 AS cells) generated by antisense‐mediated gene inactivation also exhibit markedly delayed differentiation; most of them showed no sign of aggregation and remained as round‐shaped single cells even after 16 h of incubation (Hosoya et al. 2003).…”

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confidence: 99%

Cell‐cycle checkpoint for transition from cell division to differentiation

Maeda¹

2011

Dev Growth Differ

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In general, growth and differentiation are mutually exclusive, but they are cooperatively regulated during the course of development. Thus, the process of a cell's transition from growth to differentiation is of general importance for the development of organisms, and terminally differentiated cells such as nerve cells never divide. Meanwhile, the growth rate speeds up when cells turn malignant. The cellular slime mold Dictyostelium discoideum grows and multiplies as long as nutrients are supplied, and its differentiation is triggered by starvation. A critical checkpoint (growth ⁄ differentiation transition or GDT point), from which cells start differentiating in response to starvation, has been precisely specified in the cell cycle of D. discoideum Ax-2 cells. Accordingly, integration of GDT point-specific events with starvation-induced events is needed to understand the mechanism regulating GDTs. A variety of intercellular and intracellular signals are involved positively or negatively in the initiation of differentiation, making a series of cross-talks. As was expected from the presence of the GDT point, the cell's positioning in cell masses and subsequent cell-type choices occur depending on the cell's phase in the cell cycle at the onset of starvation. Since novel and multiple functions of mitochondria in various respects of development including the initiation of differentiation have been directly realized in Dictyostelium cells, they are also reviewed in this article.

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Unique Behavior and Function of the Mitochondrial Ribosomal Protein S4 (RPS4) in Early Dictyostelium Development

Cited by 10 publications

References 33 publications

Control of Cell Differentiation by Mitochondria, Typically Evidenced in Dictyostelium Development

Control of Cell Differentiation by Mitochondria, Typically Evidenced in Dictyostelium Development

Specific growth suppression of human cancer cells by targeted delivery of Dictyostelium mitochondrial ribosomal protein S4

Cell‐cycle checkpoint for transition from cell division to differentiation

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