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mitochondrial transcription factor A

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https://www.readbyqxmd.com/read/27913603/the-tumor-suppressor-flcn-mediates-an-alternate-mtor-pathway-to-regulate-browning-of-adipose-tissue
#1
Shogo Wada, Michael Neinast, Cholsoon Jang, Yasir H Ibrahim, Gina Lee, Apoorva Babu, Jian Li, Atsushi Hoshino, Glenn C Rowe, James Rhee, José A Martina, Rosa Puertollano, John Blenis, Michael Morley, Joseph A Baur, Patrick Seale, Zoltan Arany
Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dubé syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#2
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27906110/failed-upregulation-of-tfam-protein-and-mitochondrial-dna-in-oxidatively-deficient-fibers-of-chronic-obstructive-pulmonary-disease-locomotor-muscle
#3
Yana Konokhova, Sally Spendiff, R Thomas Jagoe, Sudhakar Aare, Sophia Kapchinsky, Norah J MacMillan, Paul Rozakis, Martin Picard, Mylène Aubertin-Leheudre, Charlotte H Pion, Jean Bourbeau, Russell T Hepple, Tanja Taivassalo
BACKGROUND: Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD). Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms. Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls...
February 18, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903899/human-mitochondrial-transcription-factors-tfam-and-tfb2m-work-synergistically-in-promoter-melting-during-transcription-initiation
#4
Aparna Ramachandran, Urmimala Basu, Shemaila Sultana, Divya Nandakumar, Smita S Patel
Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has 'post-recruitment' roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from -4 to +1 in the open complex with all three proteins and from -4 to +3 with addition of ATP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27901267/binge-alcohol-intake-after-hypergravity-stress-sustainably-decreases-ampk-and-transcription-factors-necessary-for-hepatocyte-survival
#5
Sang Gil Lee, Hong Min Wu, Chan Gyu Lee, Choong Sik Oh, So Won Chung, Sang Geon Kim
BACKGROUND: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival...
November 30, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27897991/the-double-role-of-p53-in-cancer-and-autoimmunity-and-its-potential-as-therapeutic-target
#6
REVIEW
Alessandra Fierabracci, Marsha Pellegrino
p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27897204/human-mitochondrial-transcriptional-factor-a-breaks-the-mitochondria-mediated-vicious-cycle-in-alzheimer-s-disease
#7
Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu
In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896136/attention-deficit-hyperactivity-disorder-suffers-from-mitochondrial-dysfunction
#8
Poonam Verma, Alpana Singh, Dominic Ngima Nthenge-Ngumbau, Usha Rajamma, Swagata Sinha, Kanchan Mukhopadhyay, Kochupurackal P Mohanakumar
BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. METHODS: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ(0)-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27895723/cisplatin-induced-regulation-of-signal-transduction-pathways-and-transcription-factors-in-p53-mutated-subclone-variants-of-hepatoma-cells-potential-application-for-therapeutic-targeting
#9
Jinn-Rung Kuo, Hung-Sheng Shang, Chun-Te Ho, Kun-Goung Lai, Tsan-Zon Liu, Yin-Ju Chen, Jeng-Fong Chiou
Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile antitumor effects have been demonstrated to extend beyond this narrow functional attribute. The present study determined how cisplatin regulates alternative pathways and transcription factors to exert its additional antitumor actions. Cisplatin was observed to be able to trigger an endoplasmic reticulum stress response through aggravated nitrosative stress coupled to perturbed mitochondrial calcium (Ca(2+)) homeostasis, which substantially downregulated glucose-regulated protein (GRP) 78 expression by suppressing the cleavage of activating transcription factor (ATF) 6α (90 kDa) to its active 50 kDa subunit...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894840/overexpression-of-mterf4-promotes-the-amyloidogenic-processing-of-app-by-inhibiting-adam10
#10
Xiao-Liang Wang, Qing Liu, Guo-Jun Chen, Mei-Ling Li, Yan-Hui Ding
Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) peptide in the brain, which is produced by the proteolysis of β-amyloid precursor protein (APP). Recently, the mitochondrial transcription factor 4 (MTERF4), a member of the MTERF family, was implicated in regulating mitochondrial DNA transcription and directly in controlling mitochondrial ribosomal translation. The present study identified a novel role for MTERF4 in shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4 protein were significantly increased in the hippocampus of APP/PS1 mice...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27894806/genetic-divergence-in-the-transcriptional-engram-of-chronic-alcohol-abuse-a-laser-capture-rna-seq-study-of-the-mouse-mesocorticolimbic-system
#11
Megan K Mulligan, Khyobeni Mozhui, Ashutosh K Pandey, Maren L Smith, Suzhen Gong, Jesse Ingels, Michael F Miles, Marcelo F Lopez, Lu Lu, Robert W Williams
Genetic factors that influence the transition from initial drinking to dependence remain enigmatic. Recent studies have leveraged chronic intermittent ethanol (CIE) paradigms to measure changes in brain gene expression in a single strain at 0, 8, 72 h, and even 7 days following CIE. We extend these findings using LCM RNA-seq to profile expression in 11 brain regions in two inbred strains - C57BL/6J (B6) and DBA/2J (D2) - 72 h following multiple cycles of ethanol self-administration and CIE. Linear models identified differential expression based on treatment, region, strain, or interactions with treatment...
October 15, 2016: Alcohol
https://www.readbyqxmd.com/read/27893811/the-inhibition-of-microrna-128-on-igf-1-activating-mtor-signaling-involves-in-temozolomide-induced-glioma-cell-apoptotic-death
#12
Peng-Hsu Chen, Chia-Hsiung Cheng, Chwen-Ming Shih, Kuo-Hao Ho, Cheng-Wei Lin, Chin-Cheng Lee, Ann-Jeng Liu, Cheng-Kuei Chang, Ku-Chung Chen
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#13
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27884323/the-toll-like-receptor-4-antagonist-transforming-growth-factor-%C3%AE-activated-kinase-tak-242-attenuates-taurocholate-induced-oxidative-stress-through-regulating-mitochondrial-function-in-mice-pancreatic-acinar-cells
#14
Long-Fei Pan, Lei Yu, Li-Ming Wang, Jun-Tao He, Jiang-Li Sun, Xiao-Bo Wang, Zheng-Hai Bai, Li-Juan Su, Hong-Hong Pei
BACKGROUND: Acute pancreatitis (AP) is a commonly occurring and potentially life-threatening disease. Recently, toll-like receptor 4 (TLR4) has been considered as a new clue for studying the pathogenesis of AP due to its important role in inflammatory response cascade. MATERIALS AND METHODS: The aim of this study was to investigate the potential protective effect of transforming growth factor-β-activated kinase (TAK)-242, a novel TLR4 antagonist, in taurocholate-treated mice pancreatic acinar cells...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27883062/genome-wide-transcriptome-analysis-revealed-organelle-specific-responses-to-temperature-variations-in-algae
#15
HyeonSeok Shin, Seong-Joo Hong, Chan Yoo, Mi-Ae Han, Hookeun Lee, Hyung-Kyoon Choi, Suhyung Cho, Choul-Gyun Lee, Byung-Kwan Cho
Temperature is a critical environmental factor that affects microalgal growth. However, microalgal coping mechanisms for temperature variations are unclear. Here, we determined changes in transcriptome, total carbohydrate, total fatty acid methyl ester, and fatty acid composition of Tetraselmis sp. KCTC12432BP, a strain with a broad temperature tolerance range, to elucidate the tolerance mechanisms in response to large temperature variations. Owing to unavailability of genome sequence information, de novo transcriptome assembly coupled with BLAST analysis was performed using strand specific RNA-seq data...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#16
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27881386/ppar%C3%AE-augments-heart-function-and-cardiac-fatty-acid-oxidation-in-early-experimental-polymicrobial-sepsis
#17
Stephen Wade Standage, Brock G Bennion, Taft Olpin Knowles, Dolena R Ledee, Michael A Portman, John K McGuire, W Conrad Liles, Aaron K Olson
Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of PPARα, a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild type (WT) mice over the first 24 hours of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology...
November 23, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27880996/oxidative-stress-induced-damage-to-paternal-genome-and-impact-of-meditation-and-yoga-can-it-reduce-incidence-of-childhood-cancer
#18
Dada Rima, Basant Kumar Shiv, Chawla Bhavna, Bisht Shilpa, Khan Saima
Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception...
January 9, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27878255/roles-of-mitochondrial-transcription-factor-a-and-microrna%C3%A2-590%C3%A2-3p-in-the-development-of-colon-cancer
#19
Kaiming Wu, Zhenxian Zhao, Yinglian Xiao, Jianjun Peng, Jianhui Chen, Yulong He
Mitochondrial transcription factor A (TFAM) participates in the process of mitochondrial DNA replication and transcription. microRNAs (miRNAs) serve an important role in the regulation of gene expression. However, the roles of TFAM and certain miRNAs and their associations in the development of numerous cancer types remain unclear. The current study demonstrated that the expression of TFAM was significantly upregulated in colon cancer compared with the normal tissue, while the expression of miRNA‑590‑3p (miR‑590‑3p) was predicted with a high score using miRWalk software, and the luciferase assay demonstrated that TFAM was the direct target of miRNA‑590‑3p...
November 21, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27878239/aicar-induces-mitochondrial-apoptosis-in-human-osteosarcoma-cells-through-an-ampk-dependent-pathway
#20
Masayuki Morishita, Teruya Kawamoto, Hitomi Hara, Yasuo Onishi, Takeshi Ueha, Masaya Minoda, Etsuko Katayama, Toshiyuki Takemori, Naomasa Fukase, Masahiro Kurosaka, Ryosuke Kuroda, Toshihiro Akisue
The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo...
November 21, 2016: International Journal of Oncology
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