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mitochondria in stem cells

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https://www.readbyqxmd.com/read/29054138/mdivi-1-protects-human-w8b2-cardiac-stem-cells-from-oxidative-stress-and-simulated-ischemia-reperfusion-injury
#1
Ayeshah A Rosdah, Simon T Bond, Priyadharshini Sivakumaran, Ashfaqul Hoque, Jonathan S Oakhill, Brian G Drew, Lea Md Delbridge, Shiang Yong Lim
Cardiac stem cell (CSC) therapy is a promising approach to treat ischemic heart disease. However, the poor survival of transplanted stem cells in the ischemic myocardium has been a major impediment in achieving an effective cell-based therapy against myocardial infarction. Inhibiting mitochondrial fission has been shown to promote survival of several cell types. However, the role of mitochondrial morphology in survival of human CSC remains unknown. In this study, we investigated whether Mdivi-1, an inhibitor of mitochondrial fission protein Drp1, can improve survival of a novel population of human W8B2+ CSCs in hydrogen peroxide-induced oxidative stress and simulated ischemia-reperfusion injury models...
October 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29040870/parkin-absence-accelerates-microtubule-aging-in-dopaminergic-neurons
#2
Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29036909/diabetes-induced-dysfunction-of-mitochondria-and-stem-cells-in-skeletal-muscle-and-the-nervous-system
#3
REVIEW
Shin Fujimaki, Tomoko Kuwabara
Diabetes mellitus is one of the most common metabolic diseases spread all over the world, which results in hyperglycemia caused by the breakdown of insulin secretion or insulin action or both. Diabetes has been reported to disrupt the functions and dynamics of mitochondria, which play a fundamental role in regulating metabolic pathways and are crucial to maintain appropriate energy balance. Similar to mitochondria, the functions and the abilities of stem cells are attenuated under diabetic condition in several tissues...
October 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29033320/mitophagy-controls-the-activities-of-tumor-suppressor-p53-to-regulate-hepatic-cancer-stem-cells
#4
Kai Liu, Jiyoung Lee, Ja Yeon Kim, Linya Wang, Yongjun Tian, Stephanie T Chan, Cecilia Cho, Keigo Machida, Dexi Chen, Jing-Hsiung James Ou
Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29031061/crassiflorone-derivatives-that-inhibit-trypanosoma-brucei-glyceraldehyde-3-phosphate-dehydrogenase-tbgapdh-and-trypanosoma-cruzi-trypanothione-reductase-tctr-and-display-trypanocidal-activity
#5
Elisa Uliassi, Giulia Fiorani, R Luise Krauth-Siegel, Christian Bergamini, Romana Fato, Giulia Bianchini, J Carlos Menéndez, Maria Teresa Molina, Eulogio López-Montero, Federico Falchi, Andrea Cavalli, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Carolina B Moraes, Lucio H Freitas-Junior, Chiara Borsari, Maria Paola Costi, Maria Laura Bolognesi
Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal properties, isolated from the stem bark of the African ebony tree Diospyros crassiflora. We noticed that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their potential as anti-trypanosomatid agents...
October 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29029404/quercetin-induced-ros-production-triggers-mitochondrial-cell-death-of-human-embryonic-stem-cells
#6
So-Yeon Kim, Ho-Chang Jeong, Soon-Ki Hong, Mi-Ok Lee, Seung-Ju Cho, Hyuk-Jin Cha
Small molecules to selectively induce cell death of undifferentiated human pluripotent stem cells (hPSCs) have been developed with the aim of lowering the risk of teratoma formation during hPSC-based cell therapy. In this context, we have reported that Quercetin (QC) induces cell death selectively in hESCs via p53 mitochondrial localization. However, the detailed molecular mechanism by which hESCs undergo selective cell death induced by QC remains unclear. Herein, we demonstrate that mitochondrial reactive oxygen species (ROS), strongly induced by QC in human embryonic stem cells (hESCs) but not in human dermal fibroblasts (hDFs), were responsible for QC-mediated hESC's cell death...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28985528/chromatin-and-single-cell-rna-seq-profiling-reveal-dynamic-signaling-and-metabolic-transitions-during-human-spermatogonial-stem-cell-development
#7
Jingtao Guo, Edward J Grow, Chongil Yi, Hana Mlcochova, Geoffrey J Maher, Cecilia Lindskog, Patrick J Murphy, Candice L Wike, Douglas T Carrell, Anne Goriely, James M Hotaling, Bradley R Cairns
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4(+) hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4(+) hSSCs and differentiating c-KIT(+) spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28980199/new-challenge-mitochondrial-epigenetics
#8
REVIEW
Martin Stimpfel, Nina Jancar, Irma Virant-Klun
Epigenetics can be explored at different levels and can be divided into two major areas: epigenetics of nuclear-encoded DNA and epigenetics of mitochondrial-encoded DNA. In epigenetics of nuclear-encoded DNA, the main roles are played by DNA methylation, changes in histone structure and several types of non-coding RNAs. Mitochondrial epigenetics seems to be similar in the aspect of DNA methylation and to some extent in the role of non-coding RNAs but differs significantly in changes in components coiling DNA...
October 4, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28978719/pharmacological-dual-inhibition-of-tumor-and-tumor-induced-functional-limitations-in-transgenic-model-of-breast-cancer
#9
Ruizhong Wang, Poornima Bhat-Nakshatri, Maria B Padua, Mayuri S Prasad, Manjushree Anjanappa, Max Jacobson, Courtney Finnearty, Victoria Sefcsik, Kyle McElyea, Rachael Redmond, George E Sandusky, Narsimha Penthala, Peter A Crooks, Jianguo Liu, Teresa Zimmers, Harikrishna Nakshatri
Breast cancer progression is associated with systemic effects including functional limitations and sarcopenia without the appearance of overt cachexia. Autocrine/paracrine actions of cytokines/chemokines produced by cancer cells mediate cancer progression and functional limitations. The cytokine-inducible transcription factor NF-κB could be central to this process, as it displays oncogenic functions and is integral to the Pax7:MyoD:Pgc-1β:miR-486 myogenesis axis. We tested this possibility using the MMTV-PyMT transgenic mammary tumor model and the NF-κB inhibitor dimethylaminoparthenolide (DMAPT)...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978427/myc-and-mcl1-cooperatively-promote-chemotherapy-resistant-breast-cancer-stem-cells-via-regulation-of-mitochondrial-oxidative-phosphorylation
#10
Kyung-Min Lee, Jennifer M Giltnane, Justin M Balko, Luis J Schwarz, Angel L Guerrero-Zotano, Katherine E Hutchinson, Mellissa J Nixon, Mónica V Estrada, Violeta Sánchez, Melinda E Sanders, Taekyu Lee, Henry Gómez, Ana Lluch, J Alejandro Pérez-Fidalgo, Melissa Magdalene Wolf, Gabriela Andrejeva, Jeffrey C Rathmell, Stephen W Fesik, Carlos L Arteaga
Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1...
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978032/vitamin-c-and-doxycycline-a-synthetic-lethal-combination-therapy-targeting-metabolic-flexibility-in-cancer-stem-cells-cscs
#11
Ernestina Marianna De Francesco, Gloria Bonuccelli, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti
Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by targeting mitochondrial protein translation. The expression of four mitochondrial DNA encoded proteins (MT-ND3, MT-CO2, MT-ATP6 and MT-ATP8) is suppressed, by up to 35-fold. This high selection pressure metabolically synchronizes the surviving cancer cell sub-population towards a predominantly glycolytic phenotype, resulting in metabolic inflexibility...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975370/mesenchymal-stem-cells-from-preterm-to-term-newborns-undergo-a-significant-switch-from-anaerobic-glycolysis-to-the-oxidative-phosphorylation
#12
Silvia Ravera, Marina Podestà, Federica Sabatini, Chiara Fresia, Marta Columbaro, Silvia Bruno, Ezio Fulcheri, Luca Antonio Ramenghi, Francesco Frassoni
We evaluated the energy metabolism of human mesenchymal stem cells (MSC) isolated from umbilical cord (UC) of preterm (< 37 weeks of gestational age) and term (≥ 37 weeks of gestational age) newborns, using MSC from adult bone marrow as control. A metabolic switch has been observed around the 34th week of gestational age from a prevalently anaerobic glycolysis to the oxidative phosphorylation. This metabolic change is associated with the organization of mitochondria reticulum: preterm MSCs presented a scarcely organized mitochondrial reticulum and low expression of proteins involved in the mitochondrial fission/fusion, compared to term MSCs...
October 3, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28974722/succinate-promotes-stem-cell-migration-through-the-gpr91-dependent-regulation-of-drp1-mediated-mitochondrial-fission
#13
So Hee Ko, Gee Euhn Choi, Ji Young Oh, Hyun Jik Lee, Jun Sung Kim, Chang Woo Chae, Diana Choi, Ho Jae Han
The role of metabolites produced from stem cell metabolism has been emerged as signaling molecules to regulate stem cell behaviors such as migration. The mitochondrial morphology is closely associated with the metabolic balance and stem cell function. However, the physiological role of succinate on human mesenchymal stem cell (hMSC) migration by regulating the mitochondrial morphology remains unclear. Here, we investigate the effect of succinate on hMSC migration via regulation of mitochondrial dynamics and its related signaling pathway...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28965985/dysfunctions-of-mitochondria-in-close-association-with-strong-perturbation-of-long-noncoding-rnas-expression-in-down-syndrome
#14
Jia-Jun Qiu, Yan-Na Liu, Zhao-Rui Ren, Jing-Bin Yan
Trisomy 21 is the most common chromosomal disorder and underlies Down syndrome. Epigenetics, such as DNA methylation and post-translational histone modifications, plays a vital role in Down syndrome. However, the functions of epigenetics-related long noncoding RNAs (lncRNAs), found to have an impact on neural diseases such as Alzheimer's disease, remain unknown in Down syndrome. In this study, we analyzed the RNA sequencing data from Down syndrome-induced pluripotent stem cells (iPSCs) and normal iPSCs. A large number of lncRNAs were identified differentially expressed in Down syndrome-iPSCs...
September 29, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28962889/a-new-clerodane-furano-diterpene-glycoside-from-tinospora-cordifolia-triggers-autophagy-and-apoptosis-in-hct-116-colon-cancer-cells
#15
Neha Sharma, Ashok Kumar, P R Sharma, Arem Qayum, Shashank K Singh, Prabhu Dutt, Satya Paul, Vivek Gupta, M K Verma, N K Satti, R Vishwakarma
ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia is a miraculous ayurvedic herb used in the treatment of innumerable diseases such as diabetes, gonorrhea, secondary syphilis, anaemia, rheumatoid arthritis, dermatological diseases, cancer, gout, jaundice, asthma, leprosy, in the treatment of bone fractures, liver & intestinal disorders, purifies the blood, gives new life to the whole body; (rejuvenating herb) and many more. Recent studies have revealed the anticancer potential of this plant but not much work has been done on the anticancer chemical constituents actually responsible for its amazing anticancer effects...
September 27, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28962818/bmp-2-combined-with-salvianolic-acid-b-promotes-cardiomyocyte-differentiation-of-rat-bone-marrow-mesenchymal-stem-cells
#16
Yang Lv, Chen-Wei Gao, Bo Liu, Hao-Yu Wang, Hai-Ping Wang
The present study tested the hypotheses that bone morphogenetic protein 2(BMP-2) combined with salvianolic acid B(Sal-B) enhance the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) towards cardiomyocytes in vitro. BMSCs were treated with BMP-2 and Sal-B, alone or in combination, for 72 h, then added new media (excluding inductive substance) and cultured for 4 weeks. The morphologic characteristics, surface antigens and mRNA expression of several transcription factors were also assessed. We found that they could all be identified by the positive staining for cardiomyocyte-specific proteins, desmin and cardiac troponin T, in these cells...
October 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28959184/mitophagy-failure-in-fibroblasts-and-ipsc-derived-neurons-of-alzheimer-s-disease-associated-presenilin-1-mutation
#17
Patricia Martín-Maestro, Ricardo Gargini, Andrew A Sproul, Esther García, Luis C Antón, Scott Noggle, Ottavio Arancio, Jesús Avila, Vega García-Escudero
Familial Alzheimer's disease (FAD) is clearly related with the accumulation of amyloid-beta (Aβ) and its deleterious effect on mitochondrial function is well established. Anomalies in autophagy have also been described in these patients. In the present work, functional analyses have been performed to study mitochondrial recycling process in patient-derived fibroblasts and neurons from induced pluripotent stem cells harboring the presenilin 1 mutation A246E. Mitophagy impairment was observed due to a diminished autophagy degradation phase associated with lysosomal anomalies, thus causing the accumulation of dysfunctional mitochondria labeled by Parkin RBR E3 ubiquitin protein ligase (PARK2)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28957874/fracture-healing-and-the-underexposed-role-of-extracellular-vesicle-based-crosstalk
#18
Zhi Qiao, Johannes Greven, Klemens Horst, Roman Pfeifer, Philipp Kobbe, Hans-Christoph Pape, Frank Hildebrand
The process of fracture healing is complex and requires an interaction of multiple organ systems. Cell-cell communication is known to be very important during this process. Extracellular vesicle (EVs) are small membranous vesicles generated from a variety of cells. Proteins, RNAs, small molecules and mitochondria DNA were found to be transported among cells through EVs. EV-based crosstalk represents a substantial cell-cell communication pattern, that can both interact with cells through molecular surfaces, and transfer molecules to cells...
September 27, 2017: Shock
https://www.readbyqxmd.com/read/28951556/human-ipsc-disease-modelling-reveals-functional-and-structural-defects-in-retinal-pigment-epithelial-cells-harbouring-the-m-3243a%C3%A2-%C3%A2-g-mitochondrial-dna-mutation
#19
Valeria Chichagova, Dean Hallam, Joseph Collin, Adriana Buskin, Gabriele Saretzki, Lyle Armstrong, Patrick Yu-Wai-Man, Majlinda Lako, David H Steel
The m.3243A > G mitochondrial DNA mutation was originally described in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The phenotypic spectrum of the m.3243A > G mutation has since expanded to include a spectrum of neuromuscular and ocular manifestations, including reduced vision with retinal degeneration, the underlying mechanism of which remains unclear. We used dermal fibroblasts, from patients with retinal pathology secondary to the m.3243A > G mutation to generate heteroplasmic induced pluripotent stem cell (hiPSC) clones...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28942281/antihypertrophic-effects-of-small-molecules-that-maintain-mitochondrial-atp-levels-under-hypoxia
#20
Hiroaki Nagai, Tomoko Satomi, Akiko Abiru, Kazumasa Miyamoto, Koji Nagasawa, Minoru Maruyama, Satoshi Yamamoto, Kuniko Kikuchi, Hiromitsu Fuse, Masakuni Noda, Yoshiyuki Tsujihata
Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain...
October 2017: EBioMedicine
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