Mitochondrial regulation of bone homeostasis via mitochondria transfer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE222961 | GEO | 2024/04/08
REPOSITORIES: GEO
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Project description:To reveal an unappreciated mechanism of mitochondrial regulation of skeletal metabolic homeostasis via mitochondria transfer and provide new insights of the mechanism of glucocorticoid-induced osteoporosis progression.
2024-04-08 | GSE248687 | GEO
Project description:Recent studies have demonstrated that mitochondria can be transferred between different cell types to control metabolic homeostasis. However, whether the mitochondria transfer network occurred in the skeletal system or regulate skeletal metabolic homeostasis in vivo is not fully elucidated. Herein, we found that osteolineage cells transfer mitochondria to CD11b+ myeloid, B220+ lymphoid and hematopoietic stem and progenitor cells (HSPCs), of which monocytes/macrophages received the most transferred mitochondria. This process was inhibited by GC treatment contributing to the progression of glucocorticoid-induced osteoporosis (GIOP). Further analysis demonstrated that osteolineage cells transfer mitochondria to osteoclastic lineage cells via Miro1 mediated direct contact, and altered the glutathione metabolism, leading to the ferroptosis of osteoclastic lineage cells, thus inhibiting osteoclast activities. These findings revealed an unappreciated mechanism of mitochondrial regulation of skeletal metabolic homeostasis via mitochondria transfer and provide new insights of the mechanism of GIOP progression.
2024-04-08 | GSE225414 | GEO
Project description:Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, we examined mesenchymal stem cell (MSC) regulation by macrophages in the bone marrow environment. We found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes and metabolic statuses release oxidatively damaged mitochondria. The transfer of dysfunctional mitochondria to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. We showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.
2022-09-11 | GSE198806 | GEO
Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B 0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction. time series
2011-11-22 | E-GEOD-33831 | biostudies-arrayexpress
Project description:Mesenchymal stem cells (MSCs) are cells with high regenerative and immunosuppressive capacity that are known to be very potent donors of functional mitochondria to all surrounding cells, including immune cells. As metabolism shapes immune cell response and phenotype, mitochondrial transfer might be one of the main immunosuppressive mechanisms used by stem cells. However, the precise mechanism underlying horizontal mitochondrial transfer and its effect on some cell populations has yet to be discovered. In our project, we have shown that MSCs transfer mitochondria to B lymphocytes less efficiently in comparison to other immune populations. To describe the effect of mitochondrial transfer on activated B lymphocytes, MSCs were co-cultivated with B lymphocytes which were activated prior to co-cultivation. Then B cell acceptors and non-acceptors of mitochondria were sorted for further RNA isolation and the performance of bulk RNA-seq.
2024-03-02 | E-MTAB-13438 | biostudies-arrayexpress
Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine- and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B rho0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction.
2011-11-22 | GSE33831 | GEO
Project description:Glioblastoma (GBM) cells acquire mitochondria from glial cells in vitro and in vivo. This transfer is accompanied by increased tumor-initiation capacity.
2021-08-31 | GSE183004 | GEO
Project description:Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune mediated diseases. They exert immunoregulatory and tissue restoring effects. MSCmediated transfer of mitochondria (MitoT) had been demonstrated to rescue target organs from tissue damage. While the mechanism remains to be fully resolved, we explored the effect of MitoT on lymphoid cells. Here, we describe dose dependent MitoT from mitochondria-labelled MSCs mainly to T CD4+ rather than to T CD8+ or CD19+ B-cells. Artificial transfer of isolated MSC-derived mitochondria increased the expression of mRNA transcripts involved in T cell activation and T-regulatory cell differentiation including FOXP3, IL2RA, CTLA4 and TGFβ1, leading to an increase of a highly suppressive CD25+FoxP3+ population. In a GVHD mouse model, transplantation of MitoT-induced human T cells led to significant improvement in survival and reduction in tissue damage and organ T CD4+, CD8+ and IFNγ+ expressing cell infiltration. These findings point to a unique CD4+ T cell reprogramming mechanism with pre-clinical proof of concept data that pave the way for the exploration of organelle-based therapies in immune diseases.
2019-11-16 | GSE140483 | GEO
Project description:The goals of this study were to determine the effects of lateral transfer of mitochondria on recipient cell biology. We therefore collected cancer cells with and without macrophage mitochondria, and macrophages with and without cancer cell mitochondria, and analyzed transcriptomes by single-cell RNA-sequencing. Through our analysis, we found that cancer cells that received macrophage mitochondria have an enrichment of transcripts associated with cell cycle progression compared to cancer cells without macrophage mitochondria. We further validated these findings with wet lab experiments using cell proliferation markers.
2021-08-06 | GSE181410 | GEO
Project description:In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca2+ ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determined the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER-anchored VAPB protein at MAMs. The structure of PTPIP51_TPR showed an archetypal TPR fold, and an electron density corresponding to an unidentified lipid-like molecule probably derived from the protein expression host was found in the structure. We revealed functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduced the mitochondrial cardiolipin level. Additionally, we confirmed that the PTPIP51–VAPB interaction is mediated by the FFAT-like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM-tethering function similar to the ERMES complex in yeast.
2021-03-04 | ST001717 | MetabolomicsWorkbench