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mitochondria in stem cells

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https://www.readbyqxmd.com/read/29669911/mpc1-is-essential-for-pgc-1%C3%AE-induced-mitochondrial-respiration-and-biogenesis
#1
Eunjin Koh, Young Kyung Kim, Daye Shin, Kyung-Sup Kim
Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is downregulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha (PGC-1α)...
April 18, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29661859/mitochondria-and-the-dynamic-control-of-stem-cell-homeostasis
#2
REVIEW
Pawel Lisowski, Preethi Kannan, Barbara Mlody, Alessandro Prigione
The maintenance of cellular identity requires continuous adaptation to environmental changes. This process is particularly critical for stem cells, which need to preserve their differentiation potential over time. Among the mechanisms responsible for regulating cellular homeostatic responses, mitochondria are emerging as key players. Given their dynamic and multifaceted role in energy metabolism, redox, and calcium balance, as well as cell death, mitochondria appear at the interface between environmental cues and the control of epigenetic identity...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29656925/dynamics-of-parkin-dependent-mitochondrial-ubiquitylation-in-induced-neurons-and-model-systems-revealed-by-digital-snapshot-proteomics
#3
Alban Ordureau, Joao A Paulo, Wei Zhang, Tim Ahfeldt, Jiuchun Zhang, Erin F Cohn, Zhonggang Hou, Jin-Mi Heo, Lee L Rubin, Sachdev S Sidhu, Steven P Gygi, J Wade Harper
Flux through kinase and ubiquitin-driven signaling systems depends on the modification kinetics, stoichiometry, primary site specificity, and target abundance within the pathway, yet we rarely understand these parameters and their spatial organization within cells. Here we develop temporal digital snapshots of ubiquitin signaling on the mitochondrial outer membrane in embryonic stem cell-derived neurons, and we model HeLa cell systems upon activation of the PINK1 kinase and PARKIN ubiquitin ligase by proteomic counting of ubiquitylation and phosphorylation events...
April 11, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#4
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
April 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29652044/-the-ultrastructure-of-sertoli-cells-and-spermatogonia-in-the-rats-exposed-to-radiation-under-conditions-of-therapeutic-and-prophylactic-application-of-low-intensity-electromagnetic-emission
#5
Y N Korolev, I P Bobrovnitskii, M S Geniatulina, L A Nikulina, L V Mikhailik
BACKGROUND: it has been demonstrated in various experimental studies that radiation exposure produces a negative impact on the processes of spermatogenesis associated with the disturbances of the microcirculation processes in the testes and the development of cellular and intracellular disintegration expressed as destructive changes in the cells leading to their death. AIM: The objective of the present study was to detect the ultrastructural abnormalities in the cells of Sertoli and spermatogonia under conditions of their exposure to radiation and to identify the peculiarities of their regeneration under the influence of the therapeutic and prophylactic application of low-intensity ultra-high frequency (UHF) electromagnetic radiation (EMR) and low-intensity low-frequency magnetic field (MF)...
April 9, 2018: Voprosy Kurortologii, Fizioterapii, i Lechebnoĭ Fizicheskoĭ Kultury
https://www.readbyqxmd.com/read/29650042/dental-pulp-stem-cells-used-to-deliver-the-anticancer-drug-paclitaxel
#6
Hamideh Salehi, Siham Al-Arag, Elodie Middendorp, Csilla Gergely, Frederic Cuisinier, Valerie Orti
BACKGROUND: Understanding stem cell behavior as a delivery tool in cancer therapy is essential for evaluating their future clinical potential. Previous in-vivo studies proved the use of mesenchymal stem cells (MSCs) for local delivery of the commonest anticancer drug, paclitaxel (PTX). Dental pulp is a relatively abundant noninvasive source of MSCs. We assess dental pulp stem cells (DPSCs), for the first time, as anticancer drug carriers. Confocal Raman microscopy is a unique tool to trace drug and cell viability without labeling...
April 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29650039/carbon-black-suppresses-the-osteogenesis-of-mesenchymal-stem-cells-the-role-of-mitochondria
#7
Yulai Shen, Lu Wu, Dongdong Qin, Yankai Xia, Zhu Zhou, Xuemei Zhang, Xin Wu
BACKGROUND: The rapid increase in carbon black poses threats to human health. We evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow-derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the osteogenesis of MSCs and are potential targets of nanomaterials, so we studied the role of mitochondria in the CB Printex 90-induced effects on osteogenesis. RESULTS: Low doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause deleterious effects on MSCs' viability significantly inhibited osteogenesis of MSCs...
April 12, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29625581/evaluation-of-the-effects-of-ascorbic-acid-on-metabolism-of-human-mesenchymal-stem-cells
#8
Koichi Fujisawa, Kazusa Hara, Taro Takami, Sae Okada, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29624114/ultrastructural-analysis-of-human-umbilical-cord-derived-mscs-at-undifferentiated-stage-and-during-osteogenic-and-adipogenic-differentiation
#9
Serbay Ozkan, Basak Isildar, Mahmut Oncul, Zafer Baslar, Semih Kaleli, Meral Koyuturk
Mesenchymal stem cells (MSCs) are considered as an important tool for regenerative medicine and experimental treatments. Unveiling the ultrastructural changes during the differentiation of MSCs might help us to understand the nature of the process and to develop novel therapeutic approaches. For this purpose, human umbilical cord (hUC) was chosen as MSC source. In the first place, MSCs were isolated from sub-amniotic, intervascular and perivascular areas of hUC by enzymatic and tissue explant method to determine the most favorable region of hUC and technique for further processing...
April 6, 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29620216/doxycycline-targets-aldehyde-dehydrogenase%C3%A2-positive-breast-cancer-stem-cells
#10
Chang-Ching Lin, Miao-Chia Lo, Rebecca R Moody, Nicholas O Stevers, Samantha L Tinsley, Duxin Sun
Targeting cancer stem cells (CSCs) is a key strategy to prevent cancers from developing drug resistance and metastasis. Mitochondria have been reported to be a vulnerability of CSCs by multiple studies. Here, we report that doxycycline, functioning as an inhibitor of mitochondrial biogenesis, can effectively target breast cancer stem cells (BCSCs). Our results revealed that doxycycline significantly decreased the frequency of aldehyde dehydrogenase‑positive (ALDH+) BCSCs as well as mammosphere formation efficiency in HER2+ and triple‑negative breast cancer (TNBC) subtypes...
March 27, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29618819/advanced-maturation-of-human-cardiac-tissue-grown-from-pluripotent-stem-cells
#11
Kacey Ronaldson-Bouchard, Stephen P Ma, Keith Yeager, Timothy Chen, LouJin Song, Dario Sirabella, Kumi Morikawa, Diogo Teles, Masayuki Yazawa, Gordana Vunjak-Novakovic
Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6 . However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6 . Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time...
April 4, 2018: Nature
https://www.readbyqxmd.com/read/29616191/ataxia-telangiectasia-mutated-kinase-in-the-control-of-oxidative-stress-mitochondria-and-autophagy-in-cancer-a-maestro-with-a-large-orchestra
#12
REVIEW
Venturina Stagni, Claudia Cirotti, Daniela Barilà
Ataxia-telangiectasia mutated kinase (ATM) plays a central role in the DNA damage response (DDR) and mutations in its gene lead to the development of a rare autosomic genetic disorder, ataxia telangiectasia (A-T) characterized by neurodegeneration, premature aging, defects in the immune response, and higher incidence of lymphoma development. The ability of ATM to control genome stability several pointed to ATM as tumor suppressor gene. Growing evidence clearly support a significant role of ATM, in addition to its master ability to control the DDR, as principle modulator of oxidative stress response and mitochondrial homeostasis, as well as in the regulation of autophagy, hypoxia, and cancer stem cell survival...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29611042/dysfunction-of-mesenchymal-stem-cells-isolated-from-metabolic-syndrome-and-type-2-diabetic-patients-as-result-of-oxidative-stress-and-autophagy-may-limit-their-potential-therapeutic-use
#13
REVIEW
Katarzyna Kornicka, Jenny Houston, Krzysztof Marycz
Mesenchymal stem cells (MSC) have become a promising tool for therapeutic intervention. Their unique features, including self-renewal, multipotency and immunomodulatory properties draw the worldwide attention of researchers and physicians with respect to their application in disease treatment. However, the environment (so-called niche) from which MSCs are isolated may determine their usefulness. Many studies indicated the involvement of MSCs in ageing and disease. In this review, we have focused on how type 2 diabetes (T2D) and metabolic syndrome (MS) affect MSC properties, and thus limit their therapeutic potential...
April 3, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29607684/tumor-microenvironment-on-mitochondrial-dynamics-and-chemoresistance-in-cancer
#14
Youngjin Han, Untack Cho, Soochi Kim, In Sil Park, Jae Hyun Cho, Danny N Dhanasekaran, Yong Sang Song
Mitochondria, evolutionally acquired symbionts of eukaryotic cells, are essential cytoplasmic organelles. They are structurally dynamic organelles that continually go through fission and fusion processes in response to various stimuli. Tumor tissue is composed of not just cancer cells but also various cell types like fibroblasts, mesenchymal stem and immune cells. Mitochondrial dynamics of cancer cells has been shown to be significantly affected by features of tumor microenvironment such as hypoxia, inflammation and energy deprivation...
April 2, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29604226/stem-cell-modeling-of-mitochondrial-parkinsonism-reveals-key-functions-of-opa1
#15
Mindaugas Jonikas, Martin Madill, Alexandre Mathy, Theresa Zekoll, Christos E Zois, Simon Wigfield, Marzena Kurzawa-Akanbi, Cathy Browne, David Sims, Patrick F Chinnery, Sally A Cowley, George K Tofaris
OBJECTIVE: Defective mitochondrial function due to OPA1 mutations causes primarily optic atrophy and less commonly neurodegenerative syndromes. The pathomechanism by which OPA1 mutations trigger diffuse loss of neurons in some but not all patients is unknown. Here we used a tractable iPSC-based model to capture the biology of OPA1 haploinsufficiency in cases presenting with classic eye disease versus syndromic parkinsonism. METHODS: iPSC were generated from two patients with OPA1 haploinsufficiency and two controls and differentiated into dopaminergic neurons...
March 31, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29602309/regenerative-abilities-of-mesenchymal-stem-cells-through-mitochondrial-transfer
#16
REVIEW
Swati Paliwal, Rituparna Chaudhuri, Anurag Agrawal, Sujata Mohanty
The past decade has witnessed an upsurge in studies demonstrating mitochondrial transfer as one of the emerging mechanisms through which mesenchymal stem cells (MSCs) can regenerate and repair damaged cells or tissues. It has been found to play a critical role in healing several diseases related to brain injury, cardiac myopathies, muscle sepsis, lung disorders and acute respiratory disorders. Several studies have shown that various mechanisms are involved in mitochondrial transfer that includes tunnel tube formation, micro vesicle formation, gap junctions, cell fusion and others modes of transfer...
March 30, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29582715/intercellular-mitochondria-trafficking-highlighting-the-dual-role-of-mesenchymal-stem-cells-as-both-sensors-and-rescuers-of-tissue-injury
#17
Anne-Marie Rodriguez, Jean Nakhle, Emmanuel Griessinger, Marie-Luce Vignais
Mitochondria are crucial organelles that not only regulate the energy metabolism, but also the survival and fate of eukaryotic cells. Mitochondria were recently discovered to be able to translocate from one cell to the other. This phenomenon was observed in vitro and in vivo, both in physiological and pathophysiological conditions including tissue injury and cancer. Mitochondria trafficking was found to exert prominent biological functions. In particular, several studies pointed out that this process governs some of the therapeutic effects of mesenchymal stem cells (MSCs)...
March 27, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29576218/mutations-in-pmpcb-encoding-the-catalytic-subunit-of-the-mitochondrial-presequence-protease-cause-neurodegeneration-in-early-childhood
#18
F-Nora Vögtle, Björn Brändl, Austin Larson, Manuela Pendziwiat, Marisa W Friederich, Susan M White, Alice Basinger, Cansu Kücükköse, Hiltrud Muhle, Johanna A Jähn, Oliver Keminer, Katherine L Helbig, Carolyn F Delto, Lisa Myketin, Dirk Mossmann, Nils Burger, Noriko Miyake, Audrey Burnett, Andreas van Baalen, Mark A Lovell, Naomichi Matsumoto, Maie Walsh, Hung-Chun Yu, Deepali N Shinde, Ulrich Stephani, Johan L K Van Hove, Franz-Josef Müller, Ingo Helbig
Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins...
March 21, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29575576/the-mitochondrial-unfolded-protein-response-is-activated-upon-hematopoietic-stem-cell-exit-from-quiescence
#19
Mary Mohrin, Andrew Widjaja, Yufei Liu, Hanzhi Luo, Danica Chen
The mitochondrial unfolded protein response (UPRmt ), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPRmt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPRmt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking...
March 24, 2018: Aging Cell
https://www.readbyqxmd.com/read/29568355/mitochondrial-fission-as-a-driver-of-stemness-in-tumor-cells-mdivi1-inhibits-mitochondrial-function-cell-migration-and-cancer-stem-cell-csc-signalling
#20
Maria Peiris-Pagès, Gloria Bonuccelli, Federica Sotgia, Michael P Lisanti
Mitochondria are dynamic organelles frequently undergoing fission and fusion events to maintain their integrity, bioenergetics and spatial distribution, which is fundamental to the processes of cell survival. Disruption in mitochondrial dynamics plays a role in cancer. Therefore, proteins involved in regulating mitochondrial dynamics are potential targets for treatment. mDIVI1 is an inhibitor of the mitochondrial fission protein DRP1, which induces i) mitochondrial oxidative stress and ii) effectively reduces mitochondrial metabolism...
March 2, 2018: Oncotarget
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