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mitochondrial transcription factor A

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
Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada
Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...
March 12, 2018: Biochemical and Biophysical Research Communications
Heather N Carter, Marion Pauly, Liam D Tryon, David A Hood
Mitochondrial impairments are often noted in aged skeletal muscle. The transcriptional coactivator PGC-1α is integral to maintaining mitochondria, and its expression declines in aged muscle. It remains unknown whether this is due to a transcriptional deficit during aging. Our study examined PGC-1α transcription in muscle from young and old F344BN rats. Using a rat PGC-1α promoter-reporter construct, we found that PGC-1α transcription was reduced by ~65% in aged TA muscle, accompanied by decreases in PGC-1α mRNA and transcript stability...
March 15, 2018: Journal of Applied Physiology
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
Maryam Ahmadian, Sihao Liu, Shannon M Reilly, Nasun Hah, Weiwei Fan, Eiji Yoshihara, Pooja Jha, C Daniel De Magalhaes Filho, Sandra Jacinto, Andrew V Gomez, Yang Dai, Ruth T Yu, Christopher Liddle, Annette R Atkins, Johan Auwerx, Alan R Saltiel, Michael Downes, Ronald M Evans
Brown adipose tissue (BAT) adaptively transfers energy from glucose and fat into heat by inducing a gene network that uncouples mitochondrial electron transport. However, the innate transcription factors that enable the rapid adaptive response of BAT are unclear. Here, we identify estrogen-related receptor gamma (ERRγ) as a critical factor for maintaining BAT identity. ERRγ is selectively expressed in BAT versus WAT, in which, in the absence of PGC1α, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i...
March 13, 2018: Cell Reports
Sellappan Selvaraju, Sivashanmugam Parthipan, Lakshminarayana Somashekar, B Krishnan Binsila, Atul P Kolte, Arunachalam Arangasamy, Janivara Parameshwaraiah Ravindra, Stephen A Krawetz
With artificial insemination (AI) and other precision dependent assisted reproductive technologies (ART) being followed in large scale in human and animal reproduction, assessing semen quality and fertilizability is under continuous scrutiny. Various tests have been developed to predict semen quality, but so far no single, highly reliable test is available. In this regard, transcriptomic profiling of spermatozoa assumes significance as it carries the information about spermatogenesis, sperm function, and paternal roles in post-fertilization events...
March 14, 2018: Systems Biology in Reproductive Medicine
Robert James Shute, Matthew William Heesch, Roksana Barbara Zak, Jodi L Kreiling, Dustin R Slivka
PGC-1α mRNA is increased with both exercise and exposure to cold temperature. However, transcriptional control has yet to be examined during exercise in the cold. Additionally, the need for environmental cold exposure after exercise may not be a practical recovery modality. The purpose of this study was to determine mitochondrial-related gene expression and transcriptional control of PGC-1α following exercise in a cold compared to room temperature environment. Eleven recreationally trained males completed two 1-h cycling bouts in a cold (7 {degree sign}C) or room temperature (20 {degree sign}C) environment followed by 3 h of supine recovery in standard room conditions...
March 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Saki Hirofuji, Yuta Hirofuji, Hiroki Kato, Keiji Masuda, Haruyoshi Yamaza, Hiroshi Sato, Fumiko Takayama, Michiko Torio, Yasunari Sakai, Shouichi Ohga, Tomoaki Taguchi, Kazuaki Nonaka
Rett syndrome is an X-linked neurodevelopmental disorder associated with psychomotor impairments, autonomic dysfunctions and autism. Patients with Rett syndrome have loss-of-function mutations in MECP2, the gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormal biogenic amine signaling and mitochondrial function have been found in patients with Rett syndrome; however, few studies have analyzed the association between these factors. This study investigated the functional relationships between mitochondria and the neuronal differentiation of the MeCP2-deficient stem cells from the exfoliated deciduous teeth of a child with Rett syndrome...
March 10, 2018: Biochemical and Biophysical Research Communications
Junchi Yang, Lumin Bo, Ting Han, Dan Ding, Mingming Nie, Kai Yin
Gastric cancer (GC) has a high incidence and mortality rate. If discovered late, GC tends to have a poor prognosis. Improvements in the prognostic accuracy of GC through combined analysis of multiple relevant genes and clinical factors may solve this problem. In the present study, GSE62254 (including 300 GC tissues), obtained from the Gene Expression Omnibus database, was used as a training set, and the mRNA‑sequencing data of GC (including 384 GC tissues) downloaded from the Cancer Genome Atlas database served as a validation set...
March 9, 2018: Molecular Medicine Reports
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Italo Mocchetti
Human immunodeficiency virus-1 (HIV) infection of the central nervous system promotes neuronal injury that culminates in HIV-associated neurocognitive disorders. Viral proteins, including transactivator of transcription (Tat), have emerged as leading candidates to explain HIV-mediated neurotoxicity, though the mechanisms remain unclear. Tat transgenic mice or neurons exposed to Tat, which show neuronal loss, exhibit smaller mitochondria as compared to controls. To provide an experimental clue as to which mechanisms are used by Tat to promote changes in mitochondrial morphology, rat cortical neurons were exposed to Tat (100 nM) for various time points...
December 2018: Cell Death Discovery
Rossella Titone, Meifang Zhu, Danielle M Robertson
Insulin and insulin-like growth factor-1 (IGF-1) are present in human tears and likely play an important role in mediating ocular surface homeostasis. We previously characterized the IGF-1/insulin hybrid receptor (Hybrid-R) in corneal epithelial cells and found that it was activated by IGF-1 and not insulin; and reported the novel finding that it localized to the corneal epithelial cell nucleus. Since the corneal epithelium is an insulin insensitive tissue and does not require insulin for glucose uptake, this study investigated the function of insulin in corneal epithelial cells...
March 12, 2018: Scientific Reports
Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner, Alan M Fogelman, Srinivasa T Reddy
Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue...
March 12, 2018: Cell Death & Disease
Yang Yang, Lan Luo, Xueting Cai, Yuan Fang, Jiaqi Wang, Gang Chen, Jie Yang, Qian Zhou, Xiaoyan Sun, Xiaolan Cheng, Huaijiang Yan, Wuguang Lu, Chunping Hu, Peng Cao
Oxaliplatin-induced peripheral neuropathy (OIPN) is a severe, dose-limiting toxicity associated with cancer chemotherapy. The efficacy of antioxidant administration in OIPN is debatable, as the promising preliminary results obtained with a number of antioxidants have not been confirmed in larger clinical trials. Besides its antioxidant activity, the transcription factor, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2 (Nrf2) plays a crucial role in the maintenance of mitochondrial homeostasis, and mitochondrial dysfunction is a key contributor to OIPN...
March 9, 2018: Free Radical Biology & Medicine
Damla Tas, Luca Stickley, Federico Miozzo, Rafael Koch, Nicolas Loncle, Virginie Sabado, Bettina Gnägi, Emi Nagoshi
Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson's disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila...
March 12, 2018: PLoS Genetics
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
Jeong-Min Hong, Sun-Mee Lee
AIMS: Heme oxygenase-1 (HO-1), an endogenous cytoprotective enzyme, is reported that can be localized in mitochondria under stress, contributing to preserve mitochondrial function. Mitochondrial quality control (QC) is essential to cellular health and recovery linked with redox homeostasis. Recent studies reported that phosphoglycerate mutase family member (PGAM) 5, a mitochondria-resident phosphatase, plays critical role in mitochondrial homeostasis. Therefore, we aim to investigate cytoprotective mechanisms of HO-1 in I/R-induced hepatic injury focusing on mitochondrial QC associated with PGAM5 signaling...
March 7, 2018: Life Sciences
Francesca Martorana, Daniela Gaglio, Maria Rosaria Bianco, Federica Aprea, Assunta Virtuoso, Marcella Bonanomi, Lilia Alberghina, Michele Papa, Anna Maria Colangelo
Neuronal differentiation involves extensive modification of biochemical and morphological properties to meet novel functional requirements. Reorganization of the mitochondrial network to match the higher energy demand plays a pivotal role in this process. Mechanisms of neuronal differentiation in response to nerve growth factor (NGF) have been largely characterized in terms of signaling, however, little is known about its impact on mitochondrial remodeling and metabolic function. In this work, we show that NGF-induced differentiation requires the activation of autophagy mediated by Atg9b and Ambra1, as it is disrupted by their genetic knockdown and by autophagy blockers...
March 9, 2018: Cell Death & Disease
Li Gan, Delin Ma, Min Li, Fu-Chen Yang, Robert S Rogers, Joshua L Wheatley, Lauren G Koch, Steven L Britton, John P Thyfault, Paige C Geiger, John A Stanford
Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions...
March 6, 2018: Neuroscience Letters
Megan M Senchuk, Dylan J Dues, Claire E Schaar, Benjamin K Johnson, Zachary B Madaj, Megan J Bowman, Mary E Winn, Jeremy M Van Raamsdonk
Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2...
March 9, 2018: PLoS Genetics
Vachirapong Sompakdee, Auemduan Prawan, Laddawan Senggunprai, Upa Kukongviriyapan, Papavee Samathiwat, Jaroon Wandee, Veerapol Kukongviriyapan
AIMS: Transcription factor Nrf2, which regulates the expression of cytoprotective and antioxidant enzymes, contributes to proliferation and resistance to chemotherapy in cancer. The inhibition of Nrf2 can sensitize cholangiocarcinoma (CCA) cells to the cytotoxicity of several chemotherapeutic agents. In this study, we investigated the mechanism of this chemosensitizing effect. MAIN METHODS: KKU-100 cells were used in the study. Nrf2 expression was knocked down by siRNA and expression was validated by reverse transcription and polymerase chain reaction...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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