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https://www.readbyqxmd.com/read/28430591/poly-adenosine-diphosphate-ribose-polymerase-as-therapeutic-target-lessons-learned-from-its-inhibitors
#1
REVIEW
Anna Mária Cseh, Zsolt Fábián, Balázs Sümegi, Luca Scorrano
Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide to a variety of target proteins. Although they have been considered as resident nuclear elements of the DNA repair machinery, recent works revealed a more intricate physiologic role of poly(ADP-ribose) polymerases with numerous extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in fundamental cellular processes like chromatin remodelling, transcription or regulation of the cell-cycle...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429249/are-there-moral-differences-between-maternal-spindle-transfer-and-pronuclear-transfer
#2
César Palacios-González
This paper examines whether there are moral differences between the mitochondrial replacement techniques that have been recently developed in order to help women afflicted by mitochondrial DNA diseases to have genetically related children absent such conditions: maternal spindle transfer (MST) and pronuclear transfer (PNT). Firstly, it examines whether there is a moral difference between MST and PNT in terms of the divide between somatic interventions and germline interventions. Secondly, it considers whether PNT and MST are morally distinct under a therapy/creation optic...
April 20, 2017: Medicine, Health Care, and Philosophy
https://www.readbyqxmd.com/read/28418037/mitochondrial-c11orf83-is-a-potent-antiviral-protein-independent-of-interferon-production
#3
Yun Yang, Shaoquan Xiong, Bei Cai, Hui Luo, E Dong, Qiqi Li, Gaili Ji, Chengjian Zhao, Yanjun Wen, Yuquan Wei, Hanshuo Yang
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417315/disruption-of-energy-transfer-and-redox-status-by-sulfite-in-hippocampus-striatum-and-cerebellum-of-developing-rats
#4
Leonardo de Moura Alvorcem, Mateus Struecker da Rosa, Nícolas Manzke Glänzel, Belisa Parmeggiani, Mateus Grings, Felipe Schmitz, Angela T S Wyse, Moacir Wajner, Guilhian Leipnitz
Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities, whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase (CK) activity, mitochondrial respiration and redox status in hippocampus, striatum and cerebellum of developing rats. Our in vitro results showed that sulfite and thiosulfate decreased CK activity, whereas sulfite also increased malondialdehyde (MDA) levels in all brain structures evaluated...
April 17, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28416471/chemotherapy-resistant-human-acute-myeloid-leukemia-cells-are-not-enriched-for-leukemic-stem-cells-but-require-oxidative-metabolism
#5
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/28409855/the-mobility-of-mitochondria-intercellular-trafficking-in-health-and-disease
#6
Michael V Berridge, Jiri Neuzil
The view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells grow tumours only after acquiring mtDNA from cells in the local microenvironment resulting in respiration recovery, tumorigenesis and metastasis...
April 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28401922/the-phosphatidylcholine-transfer-protein-stard7-is-required-for-mitochondrial-and-epithelial-cell-homeostasis
#7
Li Yang, Cheng-Lun Na, Shiyu Luo, David Wu, Simon Hogan, Taosheng Huang, Timothy E Weaver
Mitochondria synthesize select phospholipids but lack the machinery for synthesis of the most abundant mitochondrial phospholipid, phosphatidylcholine (PC). Although the phospholipid transfer protein Stard7 promotes uptake of PC by mitochondria, the importance of this pathway for mitochondrial and cellular homeostasis represents a significant knowledge gap. Haploinsufficiency for Stard7 is associated with significant exacerbation of allergic airway disease in mice, including an increase in epithelial barrier permeability...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396924/non-introgressive-genome-chimerisation-by-malsegregation-in-autodiploidised-allotetraploids-during-meiosis-of-saccharomyces-kudriavzevii-x-saccharomyces-uvarum-hybrids
#8
Edina Karanyicz, Zsuzsa Antunovics, Z Kallai, M Sipiczki
Saccharomyces strains with chimerical genomes consisting of mosaics of the genomes of different species ("natural hybrids") occur quite frequently among industrial and wine strains. The most widely endorsed hypothesis is that the mosaics are introgressions acquired via hybridisation and repeated backcrosses of the hybrids with one of the parental species. However, the interspecies hybrids are sterile, unable to mate with their parents. Here, we show by analysing synthetic Saccharomyces kudriavzevii x Saccharomyces uvarum hybrids that mosaic (chimeric) genomes can arise without introgressive backcrosses...
April 10, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28396619/the-complete-mitogenome-of-orcula-dolium-draparnaud-1801-ultra-deep-sequencing-from-a-single-long-range-pcr-using-the-ion-torrent-pgm
#9
D S J Groenenberg, J Harl, E Duijm, E Gittenberger
BACKGROUND: With the increasing capacity of present-day next-generation sequencers the field of mitogenomics is rapidly changing. Enrichment of the mitochondrial fraction, is no longer necessary for obtaining mitogenomic data. Despite the benefits, shotgun sequencing approaches also have disadvantages. They do not guarantee obtaining the complete mitogenome, generally require larger amounts of input DNA and coverage is low compared to sequencing with enrichment strategies. If the mitogenome could be amplified in a single amplification, additional time and costs for sample preparation might outweigh these disadvantages...
2017: Hereditas
https://www.readbyqxmd.com/read/28394261/folate-cycle-enzyme-mthfd1l-confers-metabolic-advantages-in-hepatocellular-carcinoma
#10
Derek Lee, Iris Ming-Jing Xu, David Kung-Chun Chiu, Robin Kit-Ho Lai, Aki Pui-Wah Tse, Lynna Lan Li, Cheuk-Ting Law, Felice Ho-Ching Tsang, Larry Lai Wei, Cerise Yuen-Ki Chan, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Cancer cells preferentially utilize glucose and glutamine, which provide macromolecules and antioxidants that sustain rapid cell division. Metabolic reprogramming in cancer drives an increased glycolytic rate that supports maximal production of these nutrients. The folate cycle, through transfer of a carbon unit between tetrahydrofolate and its derivatives in the cytoplasmic and mitochondrial compartments, produces other metabolites that are essential for cell growth, including nucleotides, methionine, and the antioxidant NADPH...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28392448/effect-of-nitric-oxide-to-axonal-degeneration-in-multiple-sclerosis-via-downregulating-monocarboxylate-transporter-1-in-oligodendrocytes
#11
REVIEW
Xiaoyi Tang, Minghong Lan, Mao Zhang, Zhongxiang Yao
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Axonal degeneration, one of the main pathological characteristics of MS, is affected by nitric oxide (NO). In turn, NO induces mitochondrial dysfunction of neurons and glial cells. Inadequate glucose causes monocarboxylate transporter 1 (MCT1) to transfer lactate from oligodendrocytes (OLs) to neurons, which decreases MCT1 and results in energy substrate deficit (mainly lactate) in axons. The condition gradually leads to axonal degeneration...
April 6, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28387858/mitochondrial-dna-quantification-as-a-tool-for-embryo-viability-assessment-retrospective-analysis-of-data-from-single-euploid-blastocyst-transfers
#12
K Ravichandran, C McCaffrey, J Grifo, A Morales, M Perloe, S Munne, D Wells, E Fragouli
STUDY QUESTION: Does the amount of mitochondrial DNA (mtDNA) in blastocyst biopsy specimens have the potential to serve as a biomarker of euploid embryo implantation ability, independent of morphology? SUMMARY ANSWER: The results of this study strongly suggest that elevated mtDNA levels, above a previously defined threshold, are strongly associated with blastocyst implantation failure and represent an independent biomarker of embryo viability. WHAT IS KNOWN ALREADY: Improved methods of embryo selection are highly desirable in order to increase the efficiency of IVF treatment...
April 6, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28387379/relationship-between-porcine-sperm-motility-and-sperm-enzymatic-activity-using-paper-based-devices
#13
Koji Matsuura, Han-Wei Huang, Ming-Cheng Chen, Yu Chen, Chao-Min Cheng
Mammalian sperm motility has traditionally been analyzed to determine fertility using computer-assisted semen analysis (CASA) systems. To develop low-cost and robust male fertility diagnostics, we created a paper-based MTT assay and used it to estimate motile sperm concentration. When porcine sperm motility was inhibited using sperm enzyme inhibitors for sperm enzymes related to mitochondrial activity and glycolysis, we simultaneously recorded sperm motility and enzymatic reactivity using a portable motility analysis system (iSperm) and a paper-based MTT assay, respectively...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385334/live-birth-derived-from-oocyte-spindle-transfer-to-prevent-mitochondrial-disease
#14
John Zhang, Hui Liu, Shiyu Luo, Zhuo Lu, Alejandro Chávez-Badiola, Zitao Liu, Mingxue Yang, Zaher Merhi, Sherman J Silber, Santiago Munné, Michalis Konstandinidis, Dagan Wells, Taosheng Huang
Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos...
April 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28385333/first-birth-following-spindle-transfer-for-mitochondrial-replacement-therapy-hope-and-trepidation
#15
EDITORIAL
Mina Alikani, Bart C J Fauser, Juan Antonio García-Valesco, Joe Leigh Simpson, Martin H Johnson
No abstract text is available yet for this article.
April 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28380382/a-single-adaptable-cochaperone-scaffold-complex-delivers-nascent-iron-sulfur-clusters-to-mammalian-respiratory-chain-complexes-i-iii
#16
Nunziata Maio, Ki Soon Kim, Anamika Singh, Tracey A Rouault
The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28374747/mitochondrial-replacement-by-pre-pronuclear-transfer-in-human-embryos
#17
Keliang Wu, Tailai Chen, Sexin Huang, Cuiqing Zhong, Junhao Yan, Xiaoyu Zhang, Jinsong Li, Yuan Gao, Han Zhao, Zi-Jiang Chen
No abstract text is available yet for this article.
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28371286/impairment-of-preimplantation-and-postimplantation-embryonic-development-through-intrinsic-apoptotic-processes-by-ginsenoside-rg1-in-vitro-and-in-vivo
#18
Madonna Rica Anggelia, Wen-Hsiung Chan
Ginsenoside Rg1, which is the most abundant compound found in Asian ginseng (Panax ginseng), has demonstrated various pharmacological actions, including neuroprotective, immune-stimulatory, and antidiabetic effects. Pregnant women, especially in the Asian community, consume ginseng as a nutritive supplement. Thus, the effects of ginsenoside-Rg1 on embryonic development need to be investigated, such as in a mouse model. As previous investigations have found that ginsenoside Rg1 appears to either trigger or prevent apoptosis in different cell lines, the effects of this agent on apoptosis remain to be clarified...
March 29, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28369514/determination-of-glucose-deficiency-induced-cell-death-by-mitochondrial-atp-generation-driven-proton-homeostasis
#19
Yanfen Cui, Yuanyuan Wang, Miao Liu, Li Qiu, Pan Xing, Xin Wang, Guoguang Ying, Binghui Li
Glucose is one of major nutrients and its catabolism provides energy and/or building bricks for cell proliferation. Glucose deficiency results in cell death. However, the underlying mechanism still remains elusive. By using our recently developed method to monitor real-time cellular apoptosis and necrosis, we show that glucose deprivation can directly elicit necrosis, which is promoted by mitochondrial impairment, depending on mitochondrial adenosine triphosphate (ATP) generation instead of ATP depletion. We demonstrate that glucose metabolism is the major source to produce protons...
March 25, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28366985/prosaposin-knockdown-in-caco-2-cells-decreases-cellular-levels-of-coenzyme-q10-and-atp-and-results-in-the-loss-of-tight-junction-barriers
#20
Misato Kashiba, Masayuki Terashima, Tomofumi Sagawa, Shinichi Yoshimura, Yorihiro Yamamoto
Coenzyme Q10 (CoQ10) is a key component of the mitochondrial electron transfer chain and is one of the most important antioxidants. We previously found that glycoprotein prosaposin (Psap) binds CoQ10 in human cells. Although Psap is expressed in the intestines, its role in the gastrointestinal tract is not clear. To elucidate the role of Psap in the intestines, we established Psap knockdown (KD) Caco-2 cells, which are an intestinal epithelial cell line. Cellular CoQ10 levels decreased significantly in Psap KD Caco-2 cells as compared to parental Caco-2 cells...
March 2017: Journal of Clinical Biochemistry and Nutrition
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