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https://www.readbyqxmd.com/read/29764251/future-of-human-mitochondrial-dna-editing-technologies
#1
N Verechshagina, N Nikitchina, Y Yamada, Н Harashima, M Tanaka, K Orishchenko, I Mazunin
ATP and other metabolites, which are necessary for the development, maintenance, and functioning of bodily cells are all synthesized in the mitochondria. Multiple copies of the genome, present within the mitochondria, together with its maternal inheritance, determine the clinical manifestation and spreading of mutations in mitochondrial DNA (mtDNA). The main obstacle in the way of thorough understanding of mitochondrial biology and the development of gene therapy methods for mitochondrial diseases is the absence of systems that allow to directly change mtDNA sequence...
May 15, 2018: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/29747444/mitochondria-transcription-factor-a-a-putative-target-for-the-effect-of-melatonin-on-u87mg-malignant-glioma-cell-line
#2
Daiane G Franco, Isabele F Moretti, Suely K N Marie
The disruption of mitochondrial activity has been associated with cancer development because it contributes to regulating apoptosis and is the main source of reactive oxygen species (ROS) production. Mitochondrial transcription factor A (TFAM) is a protein that maintains mitochondrial DNA (mtDNA) integrity, and alterations in its expression are associated with mitochondrial damage and cancer development. In addition, studies have shown that mitochondria are a known target of melatonin, the pineal gland hormone that plays an important anti-tumorigenic role...
May 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29745247/mitochondrial-dna-phylogenetic-information-and-the-reconstruction-of-human-population-history-the-south-american-case
#3
María Bárbara Postillone, S Ivan Perez
Mitochondrial DNA (mtDNA) sequences are becoming increasingly important in the study of human population history. Here, we explore the differences in the amount of information of different mtDNA regions and their utility for the reconstruction of South American population history. We analyzed six data sets comprising 259 mtDNA sequences from South America: Complete mtDNA, Coding, Control, hypervariable region I (HVRI), Control plus cytochrome b (cytb), and cytb plus 12S plus 16S. The amount of information in each data set was estimated employing several site-by-site and haplotype-based statistics, distances among sequences, neighbor-joining trees, distances among the estimated trees, Bayesian skyline plots, and phylogenetic informativeness profiles...
July 2017: Human Biology
https://www.readbyqxmd.com/read/29743484/released-mitochondrial-dna-following-intestinal-ischemia-reperfusion-induces-the-inflammatory-response-and-gut-barrier-dysfunction
#4
Qiongyuan Hu, Huajian Ren, Jianan Ren, Qinjie Liu, Jie Wu, Xiuwen Wu, Guanwei Li, Gefei Wang, Guosheng Gu, Kun Guo, Zhiwu Hong, Song Liu, Jieshou Li
Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740017/atoh1-rfx1-rfx3-transcription-factors-facilitate-the-differentiation-and-characterisation-of-inner-ear-hair-cell-like-cells-from-patient-specific-induced-pluripotent-stem-cells-harbouring-a8344g-mutation-of-mitochondrial-dna
#5
Yen-Chun Chen, Chia-Ling Tsai, Yau-Huei Wei, Yu-Ting Wu, Wei-Ting Hsu, Hung-Ching Lin, Yi-Chao Hsu
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles...
April 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29737276/molecular-identification-and-characterization-of-sarcocystis-spp-in-horsemeat-and-beef-marketed-in-japan
#6
Rie Murata, Jun Suzuki, Ayako Hyuga, Takayuki Shinkai, Kenji Sadamasu
Human Sarcocystis infections are known to be caused by the ingestion of raw or undercooked beef or pork containing mature sarcocysts of Sarcocystis hominis or S. suihominis, respectively. In addition, several cases of parasitic food poisoning in Japan have recently been reported after consumption of raw horsemeat containing sarcocysts of S. fayeri. In this study, the presence of sarcocysts in 28 horsemeat and 121 beef samples collected in Tokyo was investigated. Sarcocysts of S. fayeri were found in 16 horsemeat samples...
2018: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/29730480/optimised-detection-of-mitochondrial-dna-strand-breaks
#7
Rebecca Hanna, Jonathan M Crowther, Pallav A Bulsara, Xuying Wang, David J Moore, Mark A Birch-Machin
Intrinsic and extrinsic factors that induce cellular oxidative stress damage tissue integrity and promote ageing, resulting in accumulative strand breaks to the mitochondrial DNA (mtDNA) genome. Limited repair mechanisms and close proximity to superoxide generation make mtDNA a prominent biomarker of oxidative damage. Using human DNA we describe an optimised long-range qPCR methodology that sensitively detects mtDNA strand breaks relative to a suite of short mitochondrial and nuclear DNA housekeeping amplicons, which control for any variation in mtDNA copy number...
May 3, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29729571/the-differential-effects-of-microcystin-lr-on-mitochondrial-dna-in-the-hippocampus-and-cerebral-cortex
#8
Xiaofen Wang, Lizhi Xu, Xinxiu Li, Jingwen Chen, Wei Zhou, Jiapeng Sun, Yaping Wang
Microcystin-LR (MC-LR) is the most abundant toxicant among microcystin variants produced by cyanobacteria. MC-induced toxicity is broadly reported to pose a threat to aquatic animals and humans and has been associated with the dysfunction of some organs such as liver and kidney. However, MC-induced neurotoxicity has not been well characterized after long-term exposure. This study was designed to investigate the neurotoxic effects after chronic oral administration of MC-LR. In our trial, C57/BL6 mice received MC-LR at 0, 1, 5, 10, 20 and 40 μg/L in drinking water for twelve months...
May 2, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29722878/global-dna-methylation-synergistically-regulates-the-nuclear-and-mitochondrial-genomes-in-glioblastoma-cells
#9
Xin Sun, Jacqueline Johnson, Justin C St John
Replication of mitochondrial DNA is strictly regulated during differentiation and development allowing each cell type to acquire its required mtDNA copy number to meet its specific needs for energy. Undifferentiated cells establish the mtDNA set point, which provides low numbers of mtDNA copy but sufficient template for replication once cells commit to specific lineages. However, cancer cells, such as those from the human glioblastoma multiforme cell line, HSR-GBM1, cannot complete differentiation as they fail to enforce the mtDNA set point and are trapped in a 'pseudo-differentiated' state...
May 2, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29719618/onc201-kills-breast-cancer-cells-in-vitro-by-targeting-mitochondria
#10
Yoshimi Endo Greer, Natalie Porat-Shliom, Kunio Nagashima, Christina Stuelten, Dan Crooks, Vishal N Koparde, Samuel F Gilbert, Celia Islam, Ashley Ubaldini, Yun Ji, Luca Gattinoni, Ferri Soheilian, Xiantao Wang, Markus Hafner, Jyoti Shetty, Bao Tran, Parthav Jailwala, Maggie Cam, Martin Lang, Donna Voeller, William C Reinhold, Vinodh Rajapakse, Yves Pommier, Roberto Weigert, W Marston Linehan, Stanley Lipkowitz
We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719607/endonuclease-g-promotes-mitochondrial-genome-cleavage-and-replication
#11
Rahel Stefanie Wiehe, Boris Gole, Laurent Chatre, Paul Walther, Enrico Calzia, Miria Ricchetti, Lisa Wiesmüller
Endonuclease G (EndoG) is a nuclear-encoded endonuclease, mostly localised in mitochondria. In the nucleus EndoG participates in site-specific cleavage during replication stress and genome-wide DNA degradation during apoptosis. However, the impact of EndoG on mitochondrial DNA (mtDNA) metabolism is poorly understood. Here, we investigated whether EndoG is involved in the regulation of mtDNA replication and removal of aberrant copies. We applied the single-cell mitochondrial Transcription and Replication Imaging Protocol (mTRIP) and PCR-based strategies on human cells after knockdown/knockout and re-expression of EndoG...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29718255/mitochondrial-dna-is-a-pro-inflammatory-damage-associated-molecular-pattern-released-during-active-ibd
#12
Ray K Boyapati, David A Dorward, Arina Tamborska, Rahul Kalla, Nicholas T Ventham, Mary K Doherty, Philip D Whitfield, Mohini Gray, Joseph Loane, Adriano G Rossi, Jack Satsangi, Gwo-Tzer Ho
Background: Due to common evolutionary origins, mitochondrial DNA (mtDNA) shares many similarities with immunogenic bacterial DNA. MtDNA is recognized as a pro-inflammatory damage-associated molecular pattern (DAMP) with a pathogenic role in several inflammatory diseases. We hypothesised that mtDNA is released during active disease, serving as a key pro-inflammatory factor in inflammatory bowel disease (IBD). Methods: Between 2014 and 2015, we collected plasma separated within 2 hours of sampling from 97 prospectively recruited IBD patients (67 ulcerative colitis [UC] and 30 Crohn's disease [CD]) and 40 non-IBD controls...
May 1, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29709472/activation-of-tgr5-promotes-mitochondrial-biogenesis-in-human-aortic-endothelial-cells
#13
Lijun Zhao, Shifang Zhang
Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs)...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29707430/genetic-divergence-and-fine-scale-population-structure-of-the-common-bottlenose-dolphin-tursiops-truncatus-montagu-found-in-the-gulf-of-guayaquil-ecuador
#14
Rosa de Los Ángeles Bayas-Rea, Fernando Félix, Rommel Montufar
The common bottlenose dolphin, Tursiops truncatus , is widely distributed along the western coast of South America. In Ecuador, a resident population of bottlenose dolphins inhabits the inner estuarine area of the Gulf of Guayaquil located in the southwestern part of the country and is under threat from different human activities in the area. Only one genetic study on South American common bottlenose dolphins has been carried out to date, and understanding genetic variation of wildlife populations, especially species that are identified as threatened, is crucial for defining conservation units and developing appropriate conservation strategies...
2018: PeerJ
https://www.readbyqxmd.com/read/29703264/cerebrospinal-fluid-mitochondrial-dna-in-neuromyelitis-optica-spectrum-disorder
#15
Kazuya Yamashita, Makoto Kinoshita, Katsuichi Miyamoto, Akiko Namba, Mikito Shimizu, Toru Koda, Tomoyuki Sugimoto, Yuki Mori, Yoshichika Yoshioka, Yuji Nakatsuji, Atsushi Kumanogoh, Susumu Kusunoki, Hideki Mochizuki, Tatsusada Okuno
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system. Although complement-dependent astrocyte damage mediated by anti-aquaporin 4 autoantibody (AQP4-Ab) is well acknowledged to be the core of NMOSD pathogenesis, additional inflammatory cascades may contribute to the establishment of lesion formation. Thus, in this study, we investigated the possible pathogenic role of immune-reactive mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) of NMOSD patients...
April 27, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29690168/a-new-species-of-brachycephalus-anura-brachycephalidae-from-the-coast-of-santa-catarina-state-southern-atlantic-forest-brazil
#16
Juliane Petry De Carli Monteiro, Thais Helena Condez, Paulo Christiano De Anchietta Garcia, EstevÃo Jasper Comitti, Ivan Borel Amaral, CÉlio Fernando Baptista Haddad
We describe a new species of Brachycephalus from municipality of São Francisco do Sul and municipality of Itapoá, in the state of Santa Catarina, Brazil, southern Atlantic Forest. The new species is known from six localities from near sea level up to 250 meters and represents the first record of a "pumpkin-toadlet" occurring in the lowlands. Morphological traits and phylogenetic analysis of a fragment the 16S mtDNA gene place the new species in the Brachycephalus pernix group. The new species is supported by external morphology, osteology, advertisement call, and mtDNA divergence...
April 12, 2018: Zootaxa
https://www.readbyqxmd.com/read/29684851/mitochondrial-dna-content-reduction-induces-aerobic-glycolysis-and-reversible-resistance-to-drug-induced-apoptosis-in-sw480-colorectal-cancer-cells
#17
Jing-Jing Mou, Jin Peng, Ying-Ying Shi, Na Li, You Wang, Yuan Ke, Yun-Feng Zhou, Fu-Xiang Zhou
Mutations and reductions in mitochondrial DNA (mtDNA), which are frequent in human tumors, may contribute to enhancing their malignant phenotypes. However, the effects of mtDNA abnormalities in colorectal cancer remain largely unknown. In this study, mtDNA-reduced cell model was established by partial depletion of mtDNA in SW480 cells and the effects of mtDNA reduction in colorectal cancer cells were investigated. We found that mtDNA-reduced cells had enhanced glucose uptake and generated markedly higher level of lactate...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29681138/the-genome-of-an-ancient-rouran-individual-reveals-an-important-paternal-lineage-in-the-donghu-population
#18
Jiawei Li, Ye Zhang, Yongbin Zhao, Yongzhi Chen, A Ochir, Sarenbilige, Hong Zhu, Hui Zhou
OBJECTIVES: Following the Xiongnu and Xianbei, the Rouran Khaganate (Rouran) was the third great nomadic tribe on the Mongolian Steppe. However, few human remains from this tribe are available for archaeologists and geneticists to study, as traces of the tombs of these nomadic people have rarely been found. In 2014, the IA-M1 remains (TL1) at the Khermen Tal site from the Rouran period were found by a Sino-Mongolian joint archaeological team in Mongolia, providing precious material for research into the genetic imprint of the Rouran...
April 21, 2018: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/29679277/the-role-of-mitochondrial-dna-damage-at-skeletal-muscle-oxidative-stress-on-the-development-of-type-2-diabetes
#19
Julia Matzenbacher Dos Santos, Denise Silva de Oliveira, Marcos Lazaro Moreli, Sandra Aparecida Benite-Ribeiro
Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced)...
April 20, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29679259/dna-methylation-a-potential-source-of-mitochondria-dna-base-mismatch-in-the-development-of-diabetic-retinopathy
#20
Manish Mishra, Renu A Kowluru
In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy...
April 21, 2018: Molecular Neurobiology
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