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https://www.readbyqxmd.com/read/28436968/metabolic-control-of-primed-human-pluripotent-stem-cell-fate-and-function-by-the-mir-200c-sirt2-axis
#1
Young Cha, Min-Joon Han, Hyuk-Jin Cha, Janet Zoldan, Alison Burkart, Jin Hyuk Jung, Yongwoo Jang, Chun-Hyung Kim, Ho-Chang Jeong, Byung-Gyu Kim, Robert Langer, C Ronald Kahn, Leonard Guarente, Kwang-Soo Kim
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28424233/cluh-couples-mitochondrial-distribution-to-the-energetic-and-metabolic-status
#2
Jamal Wakim, David Goudenege, Rodolphe Perrot, Naig Gueguen, Valerie Desquiret-Dumas, Juan Manuel Chao de la Barca, Ilaria Dalla Rosa, Florence Manero, Morgane Le Mao, Stephanie Chupin, Arnaud Chevrollier, Vincent Procaccio, Dominique Bonneau, David C Logan, Pascal Reynier, Guy Lenaers, Salim Khiati
Mitochondrial dynamics and distribution are critical in supplying ATP in response to energy demand. CLUH is a protein involved in mitochondrial distribution, whose dysfunction leads to mitochondrial clustering, the metabolic consequences of which remain unknown. To gain insight into the role of CLUH on mitochondrial energy production and cellular metabolism, we have generated CLUH knockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a smaller cell size, and with decreased abundance of respiratory complexes, resulting in OXPHOS defects...
April 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28416963/mitochondrial-acclimation-potential-to-ocean-acidification-and-warming-of-polar-cod-boreogadus-saida-and-atlantic-cod-gadus-morhua
#3
Elettra Leo, Kristina L Kunz, Matthias Schmidt, Daniela Storch, Hans-O Pörtner, Felix C Mark
BACKGROUND: Ocean acidification and warming are happening fast in the Arctic but little is known about the effects of ocean acidification and warming on the physiological performance and survival of Arctic fish. RESULTS: In this study we investigated the metabolic background of performance through analyses of cardiac mitochondrial function in response to control and elevated water temperatures and PCO2 of two gadoid fish species, Polar cod (Boreogadus saida), an endemic Arctic species, and Atlantic cod (Gadus morhua), which is a temperate to cold eurytherm and currently expanding into Arctic waters in the wake of ocean warming...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28416471/chemotherapy-resistant-human-acute-myeloid-leukemia-cells-are-not-enriched-for-leukemic-stem-cells-but-require-oxidative-metabolism
#4
Thomas Farge, Estelle Saland, Fabienne de Toni, Nesrine Aroua, Moshen Hosseini, Robin Perry, Claudie Bosc, Mayumi Sugita, Lucille Stuani, Marine Fraisse, Sarah Scotland, Clément Larrue, Héléna Boutzen, Virginie Féliu, Marie-Laure Nicolau-Travers, Stephanie Cassant-Sourdy, Nicolas Broin, Marion David, Nizar Serhan, Audrey Sarry, Suzanne Tavitian, Tony Kaoma, Laurent Vallar, Jason Iacovoni, Laetitia K Linares, Camille Montersino, Remy Castellano, Emmanuel Griessinger, Yves Collette, Olivier Duchamp, Yara Barreira, Pierre Hirsch, Tony Palama, Lara Gales, Francois Delhommeau, Barbara H Garmy-Susini, Jean-Charles Portais, Francois Vergez, Mary Selak, Gwenn Danet-Desnoyers, Martin Carroll, Christian Récher, Jean Emmanuel Sarry
Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSCs). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenograft (PDX) with cytarabine. Cytarabine residual AML cells are enriched neither in immature, quiescent cells nor LSCs. Strikingly, cytarabine-resistant pre-existing and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status...
April 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28412374/a-novel-mitochondrial-atp6-frameshift-mutation-causing-isolated-complex-v-deficiency-ataxia-and-encephalomyopathy
#5
Christopher Benjamin Jackson, Dagmar Hahn, Barbara Schröter, Uwe Richter, Brendan Battersby, Thomas Schmitt-Mechelke, Paula Martinen, Jean-Marc Nuoffer, André Schaller
We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4-year-old girl associated with ataxia, microcephaly, developmental delay and intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene was confirmed in the patient's skeletal muscle and blood. The mutation was not detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic and oxymetric analysis of the mitochondrial respiratory system in the patients' skeletal muscle and skin fibroblasts demonstrated an isolated complex V deficiency...
April 12, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28404750/human-adenine-nucleotide-translocases-physically-and-functionally-interact-with-respirasomes
#6
Ya-Wen Lu, Michelle Grace Acoba, Kandasamy Selvaraju, Tai-Chung Huang, Raja S Nirujogi, Gajanan Sathe, Akhilesh Pandey, Steven M Claypool
Members of the adenine nucleotide translocase (ANT) family exchange ADP for ATP across the mitochondrial inner membrane, an activity that is essential for oxidative phosphorylation (OXPHOS). Mutations in or dysregulation of ANTs is associated with progressive external ophthalmoplegia, cardiomyopathy, non-syndromic intellectual disability, apoptosis and the Warburg effect. Binding partners of human ANTs have not been systematically identified. The absence of such information has prevented a detailed molecular understanding of the assorted ANT-associated diseases including insight into their disparate phenotypic manifestations...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28394473/cyc1-in-ductal-carcinoma-in-situ-of-breast-associated-with-proliferation-and-comedo-necrosis
#7
Mayuko Chishiki, Kiyoshi Takagi, Ai Sato, Yasuhiro Miki, Yuta Yamamoto, Akiko Ebata, Yukiko Shibahara, Mika Watanabe, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms have remained largely unclear. Therefore, in this study, we first examined gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. CYC1 (cytochrome c1) is a subunit of complex III in the mitochondrial oxidative phosphorylation (OXPHOS) that involves in energy production...
April 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28392417/pharmacological-inhibition-of-carnitine-palmitoyltransferase-1-restores-mitochondrial-oxidative-phosphorylation-in-human-trifunctional-protein-deficient-fibroblasts
#8
Bruno Lefort, Elodie Gouache, Cécile Acquaviva, Marine Tardieu, Jean François Benoist, Jean-François Dumas, Stéphane Servais, Stéphan Chevalier, Christine Vianey-Saban, François Labartheh
BACKGROUND: Mitochondrial Trifunctional Protein deficiency (TFPD) is a severe genetic disease characterized by altered energy metabolism and accumulation of long-chain (LC) acylcarnitines in blood and tissues. This accumulation could impair the mitochondrial oxidative phosphorylation (OxPhos), contributing to the non-optimal outcome despite conventional diet therapy with medium-chain triglycerides (MCT). METHOD: Acylcarnitine and OxPhos parameters were measured in TFPD-fibroblasts obtained from 8 children and cultured in medium mimicking fasting (LCFA) or conventional treatment (MCT), with or without Etomoxir (ETX) an inhibitor of carnitine palmitoyltransferase 1 (CPT1) activity, and were compared to results obtained with fibroblasts from 5 healthy-control children...
April 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28380427/glucose-availability-controls-atf4-mediated-mitf-suppression-to-drive-melanoma-cell-growth
#9
Jennifer Ferguson, Michael Smith, Isabel Zudaire, Claudia Wellbrock, Imanol Arozarena
It is well know that cancer cells have adopted an altered metabolism and that glucose is a major source of energy for these cells. In melanoma, enhanced glucose usage is favoured through the hyper-activated MAPK pathway, which suppresses OXPHOS and stimulates glycolysis. However, it has not been addressed how glucose availability impacts on melanoma specific signaling pathways that drive melanoma cell proliferation. Here we show that melanoma cells are dependent on high glucose levels for efficient growth. Thereby, glucose metabolism controls the expression of the melanoma fate transcription factor MITF, a master regulator of melanoma cell survival and proliferation, invasion and therapy resistance...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28366030/genetic-diversities-of-mt-nd1-and-mt-nd2-genes-are-associated-with-high-altitude-adaptation-in-yak
#10
Yu Shi, Yongsong Hu, Jie Wang, Mauricio A Elzo, Xue Yang, Songjia Lai
Tibetan yak (Bos grunniens) inhabiting the Qinghai-Tibet Plateau (QTP) where the average altitude is 4000 m, is specially adapted to live at these altitudes. Conversely, cattle (B. taurus) has been found to suffer from high-altitude hypertension or heart failure when exposed to these high altitudes. Two mitochondrial genes, MT-ND1 and MT-ND2, encode two subunits of NADH dehydrogenase play an essential role in the electron transport chain of oxidative phosphorylation (OXPHOS). We sequenced these two mitochondrial genes in two bovine groups (70 Tibetan yaks and 70 Xuanhan cattle) and downloaded 300 sequences of B...
April 1, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28362806/evolved-genetic-and-phenotypic-differences-due-to-mitochondrial-nuclear-interactions
#11
Tara Z Baris, Dominique N Wagner, David I Dayan, Xiao Du, Pierre U Blier, Nicolas Pichaud, Marjorie F Oleksiak, Douglas L Crawford
The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28359291/curcumin-suppresses-gastric-tumor-cell-growth-via-ros-mediated-dna-polymerase-%C3%AE-depletion-disrupting-cellular-bioenergetics
#12
Lihua Wang, Xiwen Chen, Zhuanyun Du, Gefei Li, Mayun Chen, Xi Chen, Guang Liang, Tongke Chen
BACKGROUND: Curcumin, as a pro-apoptotic agent, is extensively studied to inhibit tumor cell growth of various tumor types. Previous work has demonstrated that curcumin inhibits cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of curcumin in regulating cellular bioenergetic processes remains largely unknown. METHODS: Western blotting and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively...
March 31, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28357370/attenuation-of-polyglutamine-induced-toxicity-by-enhancement-of-mitochondrial-oxphos-in-yeast-and-fly-models-of-aging
#13
Andrea L Ruetenik, Alejandro Ocampo, Kai Ruan, Yi Zhu, Chong Li, R Grace Zhai, Antoni Barrientos
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington's disease (HD). We have previously shown that in yeast models of HD, enhancement of mitochondrial biogenesis through overexpression of Hap4, the catalytic subunit of the transcriptional complex that regulates mitochondrial gene expression, alleviates the growth arrest induced by expanded polyglutamine (polyQ) tract peptides in rapidly dividing cells. However, the mechanism through which HAP4 overexpression exerts this protection remains unclear...
July 26, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28351484/hypocapnic-hypothesis-of-leigh-disease
#14
Ewa Pronicka
Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes. Hypocapnic hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is hypocapnia (decrease in pCO2) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28345766/%C3%AE-linolenic-acid-and-exercise-training-independently-and-additively-decreases-blood-pressure-and-prevents-diastolic-dysfunction-in-obese-zucker-rats
#15
Pierre-Andre Barbeau, Tanya M Holloway, Jamie Whitfield, Brittany Baechler, Joe Quadrilatero, Luc J C van Loon, Adrian Chabowski, Graham P Holloway
While α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms-of-action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following: control diet-sedentary (C-Sed), ALA supplemented-sedentary (ALA-Sed), control diet-exercise trained (C-Ex), or ALA supplemented-exercise trained (ALA-Ex)...
March 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28341246/anemone-rivularis-inhibits-pyruvate-dehydrogenase-kinase-activity-and-tumor-growth
#16
Tae-Wook Chung, Jung Hee Lee, Hee-Jung Choi, Mi-Ju Park, Eun-Yeong Kim, Jung Ho Han, Se Bok Jang, Syng-Ook Lee, Sang Woo Lee, Jin Hang, Li Wan Yi, Ki-Tae Ha
ETHNOPHARMACOLOGICAL RELEVANCE: Anemone rivularis Buch.-Ham. ex DC. (Ranunculaceae) have been used as a traditional remedy for treatment of inflammation and cancer. However, there is no report demonstrating experimental evidence on anti-tumor action of A. rivularis. AIM OF STUDY: The Warburg's effect, preference of aerobic glycolysis rather than oxidative phosphorylation (OXPHOS) even in oxygen rich condition, is focused as one of major characteristics of malignant tumor...
May 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28328323/an-adaptable-high-throughput-technology-enabling-the-identification-of-specific-transcription-modulators
#17
Tim Bergbrede, Emily Hoberg, Nils-Göran Larsson, Maria Falkenberg, Claes M Gustafsson
Mitochondria harbor the oxidative phosphorylation (OXPHOS) system, which under aerobic conditions produces the bulk of cellular adenosine triphosphate (ATP). The mitochondrial genome encodes key components of the OXPHOS system, and it is transcribed by the mitochondrial RNA polymerase, POLRMT. The levels of mitochondrial transcription correlate with the respiratory activity of the cell. Therefore, compounds that can increase or decrease mitochondrial gene transcription may be useful for fine-tuning metabolism and could be used to treat metabolic diseases or certain forms of cancer...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28323032/metabolic-re-wiring-of-isogenic-breast-epithelial-cell-lines-following-epithelial-to-mesenchymal-transition
#18
Skarphedinn Halldorsson, Neha Rohatgi, Manuela Magnusdottir, Kumari Sonal Choudhary, Thorarinn Gudjonsson, Erik Knutsen, Anna Barkovskaya, Bylgja Hilmarsdottir, Maria Perander, Gunhild M Mælandsmo, Steinn Gudmundsson, Óttar Rolfsson
Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28316610/integrative-approaches-for-studying-mitochondrial-and-nuclear-genome-co-evolution-in-oxidative-phosphorylation
#19
Paul Sunnucks, Hernán E Morales, Annika M Lamb, Alexandra Pavlova, Chris Greening
In animals, interactions among gene products of mitochondrial and nuclear genomes (mitonuclear interactions) are of profound fitness, evolutionary, and ecological significance. Most fundamentally, the oxidative phosphorylation (OXPHOS) complexes responsible for cellular bioenergetics are formed by the direct interactions of 13 mitochondrial-encoded and ∼80 nuclear-encoded protein subunits in most animals. It is expected that organisms will develop genomic architecture that facilitates co-adaptation of these mitonuclear interactions and enhances biochemical efficiency of OXPHOS complexes...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anemia-cells-to-glycolytic-metabolism
#20
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
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