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mitochondria in stem cells

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https://www.readbyqxmd.com/read/28337983/self-inflicted-dna-double-strand-breaks-sustain-tumorigenicity-and-stemness-of-cancer-cells
#1
Xinjian Liu, Fang Li, Qian Huang, Zhengxiang Zhang, Ling Zhou, Yu Deng, Min Zhou, Donald E Fleenor, He Wang, Michael B Kastan, Chuan-Yuan Li
DNA double-strand breaks (DSBs) are traditionally associated with cancer through their abilities to cause chromosomal instabilities or gene mutations. Here we report a new class of self-inflicted DNA DSBs that can drive tumor growth irrespective of their effects on genomic stability. We discover a mechanism through which cancer cells cause DSBs in their own genome spontaneously independent of reactive oxygen species or replication stress. In this mechanism, low-level cytochrome c leakage from the mitochondria leads to sublethal activation of apoptotic caspases and nucleases, which causes DNA DSBs...
March 24, 2017: Cell Research
https://www.readbyqxmd.com/read/28337542/%C3%AE-synuclein-binds-to-the-er-mitochondria-tethering-protein-vapb-to-disrupt-ca-2-homeostasis-and-mitochondrial-atp-production
#2
Sébastien Paillusson, Patricia Gomez-Suaga, Radu Stoica, Daniel Little, Paul Gissen, Michael J Devine, Wendy Noble, Diane P Hanger, Christopher C J Miller
α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in Parkinson's disease are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling involves close physical associations between the two organelles that are mediated by binding of the integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) to the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51)...
March 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28324490/assessment-of-mitophagy-in-ips-cell-derived-neurons
#3
Kei-Ichi Ishikawa, Akihiro Yamaguchi, Hideyuki Okano, Wado Akamatsu
Aberrant mitochondrial function is associated with many neurological diseases. Mitophagy is a key mechanism for the elimination of damaged mitochondria and maintenance of mitochondrial homeostasis. Induced pluripotent stem (iPS) cell technologies developed over the last decade have allowed us to analyze functions of the human neuron. Here we describe an efficient induction method from human iPS cells to neurons, followed by an image-based mitophagy assay.
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28319092/the-tdh-gcn5l1-fbxo15-kbp-axis-limits-mitochondrial-biogenesis-in-mouse-embryonic-stem%C3%A2-cells
#4
Valerio Donato, Massimo Bonora, Daniele Simoneschi, Davide Sartini, Yasusei Kudo, Anita Saraf, Laurence Florens, Michael P Washburn, Matthias Stadtfeld, Paolo Pinton, Michele Pagano
Self-renewing naive mouse embryonic stem cells (mESCs) contain few mitochondria, which increase in number and volume at the onset of differentiation. KBP (encoded by Kif1bp) is an interactor of the mitochondrial-associated kinesin Kif1Bα. We found that TDH, responsible for mitochondrial production of acetyl-CoA in mESCs, and the acetyltransferase GCN5L1 cooperate to acetylate Lys501 in KBP, allowing its recognition by and degradation via Fbxo15, an F-box protein transcriptionally controlled by the pluripotency core factors and repressed following differentiation...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anemia-cells-to-glycolytic-metabolism
#5
Enrico Cappelli, Paola Cuccarolo, Giorgia Stroppiana, Maurizio Miano, Roberta Bottega, Vanessa Cossu, Paolo Degan, Silvia Ravera
Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28301072/pre-conditions-for-eliminating-mitochondrial-dysfunction-and-maintaining-liver-function-after-hepatic-ischaemia-reperfusion
#6
REVIEW
Chenxia Hu, Lanjuan Li
The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood...
March 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#7
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28287607/mitoception-transferring-isolated-human-msc-mitochondria-to-glioblastoma-stem-cells
#8
Brice Nzigou Mombo, Sabine Gerbal-Chaloin, Aleksandra Bokus, Martine Daujat-Chavanieu, Christian Jorgensen, Jean-Philippe Hugnot, Marie-Luce Vignais
Mitochondria play a central role for cell metabolism, energy production and control of apoptosis. Inadequate mitochondrial function has been found responsible for very diverse diseases, ranging from neurological pathologies to cancer. Interestingly, mitochondria have recently been shown to display the capacity to be transferred between cell types, notably from human mesenchymal stem cells (MSC) to cancer cells in coculture conditions, with metabolic and functional consequences for the mitochondria recipient cells, further enhancing the current interest for the biological properties of these organelles...
February 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28283580/er-mitochondria-contacts-control-surface-glycan-expression-and-sensitivity-to-killer-lymphocytes-in-glioma-stem-like-cells
#9
Esen Yonca Bassoy, Atsuko Kasahara, Valentina Chiusolo, Guillaume Jacquemin, Emma Boydell, Sebastian Zamorano, Cristina Riccadonna, Serena Pellegatta, Nicolas Hulo, Valérie Dutoit, Madiha Derouazi, Pierre Yves Dietrich, Paul R Walker, Denis Martinvalet
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283480/leveraging-increased-cytoplasmic-nucleoside-kinase-activity-to-target-mtdna-and-oxidative-phosphorylation-in-aml
#10
Sanduni U Liyanage, Rose Hurren, Veronique Voisin, Gaëlle Bridon, Xiaoming Wang, ChangJiang Xu, Neil MacLean, Thirushi P Siriwardena, Marcela Gronda, Dana Yehudai, Shrivani Sriskanthadevan, Daina Avizonis, Aisha Shamas-Din, Mark D Minden, Gary D Bader, Rebecca Laposa, Aaron D Schimmer
Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human AML samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared to normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared to normal hematopoietic samples...
March 10, 2017: Blood
https://www.readbyqxmd.com/read/28283027/integrated-analysis-of-genetic-behavioral-and-biochemical-data-implicates-neural-stem-cell-induced-changes-in-immunity-neurotransmission-and-mitochondrial-function-in-dementia-with-lewy-body-mice
#11
Anita Lakatos, Natalie R S Goldberg, Mathew Blurton-Jones
We previously demonstrated that transplantation of murine neural stem cells (NSCs) can improve motor and cognitive function in a transgenic model of Dementia with Lewy Bodies (DLB). These benefits occurred without changes in human α-synuclein pathology and were mediated in part by stem cell-induced elevation of brain-derived neurotrophic factor (BDNF). However, instrastriatal NSC transplantation likely alters the brain microenvironment via multiple mechanisms that may synergize to promote cognitive and motor recovery...
March 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28273069/interplay-between-metabolic-identities-in-the-intestinal-crypt-supports-stem-cell-function
#12
Maria J Rodríguez-Colman, Matthias Schewe, Maaike Meerlo, Edwin Stigter, Johan Gerrits, Mia Pras-Raves, Andrea Sacchetti, Marten Hornsveld, Koen C Oost, Hugo J Snippert, Nanda Verhoeven-Duif, Riccardo Fodde, Boudewijn M T Burgering
The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5(+) crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5(+) CBCs and Paneth cells from the mouse small intestine display different metabolic programs...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28271444/the-role-of-mitochondria-in-osteogenic-adipogenic-and-chondrogenic-differentiation-of-mesenchymal-stem-cells
#13
REVIEW
Qianqian Li, Zewen Gao, Ye Chen, Min-Xin Guan
Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering due to their differentiation potential along various cell types. In recent years, accumulating evidence has suggested that the regulation of mitochondria dynamics and function is essential for successful differentiation of MSCs. In this paper, we review and provide an integrated view on the role of mitochondria in MSC differentiation. The mitochondria are maintained at a relatively low activity level in MSCs, and upon induction, mtDNA copy number, protein levels of respiratory enzymes, the oxygen consumption rate, mRNA levels of mitochondrial biogenesis-associated genes, and intracellular ATP content are increased...
March 7, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28257660/induction-of-intrinsic-apoptosis-in-leukaemia-stem-cells-and-in-vivo-zebrafish-model-by-betulonic-acid-isolated-from-walsura-pinnata-hassk-meliaceae
#14
Kok Hoong Leong, Mohamad Azrul Mahdzir, Mohd Fadzli Md Din, Khalijah Awang, Yuka Tanaka, Kasem Kulkeaw, Tohru Ishitani, Daisuke Sugiyama
BACKGROUND: Leukaemia stem cells (LSC) have been associated with disease relapse and chemotherapy resistance. Betulonic acid (BA), a pentacyclic lupane-type triterpenoid, was reported to exhibit cytotoxicity toward various cancer cells and to be capable of inducing intrinsic apoptosis in solid tumours. However, the in vitro and in vivo apoptotic effects of BA against LSC remain unknown. HYPOTHESIS/PURPOSE: We aimed to determine whether BA isolated from bark of Walsura pinnata Hassk (Meliaceae) has pro-apoptotic effects on LSC in in vitro and in vivo models...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28254309/osteo-growth-induction-titanium-surface-treatment-reduces-ros-production-of-mesenchymal-stem-cells-increasing-their-osteogenic-commitment
#15
Paolo Ghensi, Eriberto Bressan, Chiara Gardin, Letizia Ferroni, Lucio Ruffato, Mauro Caberlotto, Claudio Soldini, Barbara Zavan
Surface characteristics play a special role for the biological performance of implants and several strategies are available to this end. The OGI (Osteo Growth Induction) titanium surface is a surface, obtained by applying a strong acid onto the blasted surface. The aim of this in-vitro study is to evaluate in vitro the osteoproperties of OGI surfaces on Mesenchymal Stem cells derived from dental pulp. Our results confirm that this treatment exert a positive effect on mitochondrial homeostasis, as shown by a decrease in ROS production related to environmental stress on the mitochondria...
May 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28241143/autophagy-maintains-the-metabolism-and-function-of-young-and-old-stem-cells
#16
Theodore T Ho, Matthew R Warr, Emmalee R Adelman, Olivia M Lansinger, Johanna Flach, Evgenia V Verovskaya, Maria E Figueroa, Emmanuelle Passegué
With age, haematopoietic stem cells lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress. Here we show that loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs haematopoietic stem-cell self-renewal activity and regenerative potential...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#17
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28237394/developmental-changes-in-the-balance-of-glycolytic-atp-production-and-oxidative-phosphorylation-in-ventricular-cells-a-simulation-study
#18
Hitomi I Sano, Tamami Toki, Yasuhiro Naito, Masaru Tomita
The developmental program of the heart requires accurate regulation to ensure continuous circulation and simultaneous cardiac morphogenesis, because any functional abnormalities may progress to congenital heart malformation. Notably, energy metabolism in fetal ventricular cells is regulated in a manner that differs from adult ventricular cells: fetal cardiomyocytes generally have immature mitochondria and fetal ventricular cells show greater dependence on glycolytic ATP production. However, although various characteristics of energy metabolism in fetal ventricular cells have been reported, to our knowledge, a quantitative description of the contributions of these factors to fetal ventricular cell functions has not yet been established...
February 24, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28231483/a-novel-redox-regulator-mntnbuoe-2-pyp-5-enhances-normal-hematopoietic-stem-progenitor-cell-function
#19
Y Zhao, D W Carroll, Y You, L Chaiswing, R Wen, I Batinic-Haberle, S Bondada, Y Liang, D K St Clair
The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP(5+)(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs...
February 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28229407/assessment-of-energy-metabolic-changes-in-adipose-tissue-derived-stem-cells
#20
Ghazaleh Hajmousa, Martin C Harmsen
Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which renders ADSC a culture "artefact." The medium constituents therefore impact the efficacy of ADSC. Little attention has been paid to the energy source in medium, i.e., glucose, which feeds the cell's power plants: mitochondria...
2017: Methods in Molecular Biology
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