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mitochondrial copy number

Daniele Campa, Myrto Barrdahl, Aurelia Santoro, Gianluca Severi, Laura Baglietto, Hanane Omichessan, Rosario Tumino, H B As Bueno-de-Mesquita, Petra H Peeters, Elisabete Weiderpass, Maria-Dolores Chirlaque, Miguel Rodríguez-Barranco, Antonio Agudo, Marc Gunter, Laure Dossus, Vittorio Krogh, Giuseppe Matullo, Antonia Trichopoulou, Ruth C Travis, Federico Canzian, Rudolf Kaaks
BACKGROUND: Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC). METHODS: To gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort...
April 17, 2018: Breast Cancer Research: BCR
Te-Sha Tsai, Justin C St John
Mitochondrial DNA (mtDNA) deficient metaphase II porcine oocytes are less likely to fertilize and more likely to arrest during preimplantation development. However, they can be supplemented with autologous populations of mitochondria at the time of fertilization, which significantly increases mtDNA copy number by the 2-cell stage due to the modulation of DNA methylation at a CpG island of the gene encoding mtDNA-specific polymerase, POLG, and promotes preimplantation development. Although mitochondrial supplementation does not increase development rates or mtDNA copy number in oocytes with normal levels of mtDNA copy number, we tested whether this approach would also impact on chromosomal gene expression patterns in these oocytes at each stage of preimplantation development...
April 16, 2018: Molecular Reproduction and Development
Naoto Iwai, Kohichiroh Yasui, Akira Tomie, Yasuyuki Gen, Kei Terasaki, Tomoko Kitaichi, Tomohiro Soda, Nobuhisa Yamada, Osamu Dohi, Yuya Seko, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Hideyuki Konishi, Yuji Naito, Yoshito Itoh
The aberrant expression or alteration of microRNAs (miRNAs/miRs) contributes to the development and progression of cancer. In the present study, the functions of miR-96-5p in hepatocellular carcinoma (HCC) were investigated. It was identified that miR-96-5p expression was significantly upregulated in primary HCC tumors compared with their non-tumorous counterparts. A copy number gain was frequently observed at chromosomal region 7q32.2 in which the MIR96 locus is located, suggesting that gene amplification may be one of the mechanisms by which miR-96-5p expression is increased in HCC...
April 12, 2018: International Journal of Oncology
Bernard W M Wone, Won C Yim, Heidi Schutz, Thomas H Meek, Theodore Garland
Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNAArg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype...
April 4, 2018: Mitochondrion
Qi-Shun Wu, Qing He, Jian-Qiang He, Jun Chao, Wen-Yan Wang, Yan Zhou, Ji-Zhuang Lou, Wei Kong, Jun-Feng Chen
Left ventricular hypertrophy (LVH) is a common abnormality in hemodialysis (HD) patients. Mitochondrial dysfunction contributes to the progression of LVH. As an inner mitochondrial membrane structural protein, mitofilin plays a key role in maintaining mitochondrial structure and function. The aim of this study was to investigate the relationship between mitofilin and LVH in HD patients. A total of 98 HD patients and 32 healthy controls were included in the study. Serum N-terminal proBNP (NT-proBNP), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP) were examined...
November 2018: Renal Failure
Dong Hang, Hongmei Nan, Ane Sørlie Kværner, Immaculata De Vivo, Andrew Tan Chan, Zhibin Hu, Hongbing Shen, Edward Giovannucci, Mingyang Song
Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants...
April 4, 2018: European Journal of Epidemiology
Raúl Bonal, Enrique Vargas-Osuna, Juan Diego Mena, José Miguel Aparicio, María Santoro, Angela Martín
The quick spread of the chestnut gall wasp Dryocosmus kuriphilus in Europe constitutes an outstanding example of recent human-aided biological invasion with dramatic economic losses. We screened for the first time a set of five nuclear and mitochondrial genes from D. kuriphilus collected in the Iberian Peninsula, and compared the sequences with those available from the native and invasive range of the species. We found no genetic variability in Iberia in none of the five genes, moreover, the three genes compared with other European samples showed no variability either...
April 4, 2018: Scientific Reports
Kazuki Kansaku, Yasuhisa Munakata, Nobuhiko Itami, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
This study examined the concentration of cell-free mitochondrial DNA (cf-mtDNA) in porcine follicular fluid (FF) and explored whether the cfDNA level in the culture medium could reflect mitochondrial dysfunction in cumulus cell-oocyte complexes (COCs). cfDNA concentration was higher in the fluid of small-sized follicles, compared to that in larger follicles. The length of cfDNA ranged from short (152 bp) to long (1,914 bp) mtDNA in FF, detected by polymerase chain reaction (PCR). cfDNA concentration in FF significantly correlated with the mtDNA copy number in FF but not with the number of one-copy gene (nuclear DNA) in FF...
April 3, 2018: Journal of Reproduction and Development
Xiacheng Sun, Lei Zhan, Yibing Chen, Gang Wang, Linjie He, Qian Wang, Feng Zhou, Fang Yang, Jin Wu, Yousheng Wu, Jinliang Xing, Xianli He, Qichao Huang
Colorectal cancer is one of the leading causes of cancer death worldwide. According to global genomic status, colorectal cancer can be classified into two main types: microsatellite-stable and microsatellite-instable tumors. Moreover, the two subtypes also exhibit different responses to chemotherapeutic agents through distinctive molecular mechanisms. Recently, mitochondrial DNA depletion has been shown to induce apoptotic resistance in microsatellite-instable colorectal cancer. However, the effects of altered mitochondrial DNA copy number on the progression of microsatellite-stable colorectal cancer, which accounts for the majority of colorectal cancer, remain unclear...
2018: Signal Transduction and Targeted Therapy
Christa R Moraes, Stuart Meyers
This review summarizes current research in sperm mitochondrial function with specific emphasis on mitochondrial metabolism, reactive oxygen species production and mitochondrial genomics. This organelle is key in many crucial sperm functions including motility, hyperactivation, capacitation, acrosome reaction, and fertilization, thus its role in male fertility cannot be ignored. Recent studies have further elucidated sperm metabolism, placing greater emphasis on the importance of mitochondrial energy production for some species...
March 26, 2018: Animal Reproduction Science
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
A Mallat, L F Uchiyama, S C Lewis, R A Fredenburg, Y Terada, N Ji, J Nunnari, C C Tseng
Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential...
March 27, 2018: Biochemical and Biophysical Research Communications
Nisha Singh, Hannah McMahon, Amy Bilderbeck, Zoe E Reed, Elizabeth Tunbridge, Daniel Brett, John R Geddes, Grant C Churchill, Guy M Goodwin
OBJECTIVES: We previously demonstrated oxidative stress in bipolar patients and a relationship between the age of illness onset and total glutathione, a principal antioxidant. In this study, we sought to replicate these findings in a new cohort of patients. METHODS: We recruited bipolar patients from Warneford Hospital, Oxford, UK, of similar age and grouped them according to age of onset of illness. The early-onset group comprised patients with onset at <23 years, and the late group comprised patients with onset at >30 years...
March 30, 2018: Bipolar Disorders
Brandi L Rollins, Ling Morgan, Brooke E Hjelm, Adolfo Sequeira, Alan F Schatzberg, Jack D Barchas, Francis S Lee, Rick M Myers, Stanley J Watson, Huda Akil, Steven G Potkin, William E Bunney, Marquis P Vawter
Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA "common deletion" in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls ( p = 0...
February 2018: Molecular Neuropsychiatry
Yiyi Xu, Christian H Lindh, Bo A G Jönsson, Karin Broberg, Maria Albin
BACKGROUND: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. METHODS: We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males...
March 27, 2018: Environmental Health: a Global Access Science Source
S S-S Chen, L-P Chiu
To investigate the association between the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene Ser326Cys polymorphism and male subfertility in Taiwanese patients with varicocele, we made a prospective study. Ninety young male patients with varicocele (group 1), 50 young male patients with subclinical varicocele (group 2) and 30 normal young male patients without varicocele (group 3) were recruited in this study. The hOGG1 null homozygous genotype (Cys/Cys) and the occurrence of a 4,977-bp deletion in mitochondrial DNA and mitochondrial copy number in spermatozoa were determined by polymerase chain reaction...
March 26, 2018: Andrologia
Jingfei Zhang, Kai Wen Bai, Jintian He, Yu Niu, Yuan Lu, Lili Zhang, Tian Wang
The aim of this study was to investigate the effects of dietary curcumin supplementation on the performance, mitochondrial redox system, mitochondrial DNA (mtDNA) integrity, and antioxidant-related gene expression in the liver of broiler chickens after heat stress treatment. At day 21, a total of 400 Arbor Acres broiler chickens with similar body weight (BW) were divided into 5 groups with 8 replicates per group and then reared either at a normal temperature (22 ± 1 °C) or at a high ambient temperature (34 ± 1 °C for 8 h and 22 ± 1 °C for the remaining time) for 20 d...
March 16, 2018: Journal of Animal Science
Asmita Banerjee, Andrea Lindenmair, Simone Hennerbichler, Philipp Steindorf, Ralf Steinborn, Andrey V Kozlov, Heinz Redl, Susanne Wolbank, Adelheid Weidinger
Over a century ago, clinicians started to use the human amniotic membrane for coverage of wounds and burn injuries. To date, literally thousands of different clinical applications exist for this biomaterial almost exclusively in a decellularized or denuded form. Recent reconsiderations for the use of vital human amniotic membrane for clinical applications would take advantage of the versatile cells of embryonic origin including the entirety of their cell organelles. Recently, more and more evidence was found, showing mitochondria to be involved in most fundamental cellular processes, such as differentiation and cell death...
January 2018: Cell Transplantation
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Qiongyuan Hu, Jianan Ren, Guanwei Li, Jie Wu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Jieshou Li
Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls...
March 14, 2018: Cell Death & Disease
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