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mitochondrial biogenesis

Priyanka Maiti, Hyun-Jung Kim, Ya-Ting Tu, Antoni Barrientos
Most steps on the biogenesis of the mitochondrial ribosome (mitoribosome) occur near the mitochondrial DNA nucleoid, in RNA granules, which contain dedicated RNA metabolism and mitoribosome assembly factors. Here, analysis of the RNA granule proteome identified the presence of a set of small GTPases that belong to conserved families of ribosome assembly factors. We show that GTPBP10, a member of the conserved Obg family of P-loop small G proteins, is a mitochondrial protein and have used gene-editing technologies to create a HEK293T cell line KO for GTPBP10...
October 13, 2018: Nucleic Acids Research
Souheil-Antoine Younes, Aarthi Talla, Susan Pereira Ribeiro, Evgeniya V Saidakova, Larisa B Korolevskaya, Konstantin V Shmagel, Carey L Shive, Michael L Freeman, Soumya Panigrahi, Sophia Zweig, Robert Balderas, Leonid Margolis, Daniel C Douek, Donald D Anthony, Pushpa Pandiyan, Mark Cameron, Scott F Sieg, Leonard H Calabrese, Benigno Rodriguez, Michael M Lederman
Immune nonresponder (INR) HIV-1-infected subjects are characterized by their inability to reconstitute the CD4+ T cell pool after antiretroviral therapy. This is linked to poor clinical outcome. Mechanisms underlying immune reconstitution failure are poorly understood, although, counterintuitively, INRs often have increased frequencies of circulating CD4+ T cells in the cell cycle. While cycling CD4+ T cells from healthy controls and HIV+ patients with restored CD4+ T cell numbers complete cell division in vitro, cycling CD4+ T cells from INRs do not...
October 15, 2018: Journal of Clinical Investigation
John D Widdrington, Aurora Gomez-Duran, Angela Pyle, Marie-Helene Ruchaud-Sparagano, Jonathan Scott, Simon V Baudouin, Anthony J Rostron, Penny E Lovat, Patrick F Chinnery, A John Simpson
In order to limit the adverse effects of excessive inflammation, anti-inflammatory responses are stimulated at an early stage of an infection, but during sepsis these can lead to deactivation of immune cells including monocytes. In addition, there is emerging evidence that the up-regulation of mitochondrial quality control mechanisms, including mitochondrial biogenesis and mitophagy, is important during the recovery from sepsis and inflammation. We aimed to describe the relationship between the compensatory immune and mitochondrial responses that are triggered following exposure to an inflammatory stimulus in human monocytic cells...
2018: Frontiers in Immunology
Marzieh Rashedinia, Jamileh Saberzadeh, Tannaz Khosravi Bakhtiari, Solmaz Hozhabri, Rita Arabsolghar
Glycyrrhizic acid (GA) is the most effective ingredient in the root of licorice, with important pharmacological effects. We investigate the effects of GA on mitochondrial function and biogenesis in the aluminum toxicity in PC12 cell line. After pretreatment of PC12 cells with different concentrations of GA (5-100 μM), and specific concentration of aluminum maltolate (Almal,1000 μM) for 48 h, cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondria mass, cytochrome c oxidase enzyme activity, and the ATP level of the cells were measured...
October 13, 2018: Neurotoxicity Research
Justyna Augustyniak, Jacek Lenart, Paweł Gaj, Monika Kolanowska, Krystian Jazdzewski, Piotr Pawel Stepien, Leonora Buzanska
Bezafibrate (BZ) regulates mitochondrial biogenesis by activation of PPAR's receptors and enhancing the level of PGC-1α coactivator. In this report, we investigated the effect of BZ on the expression of genes (1) that are linked to different pathways involved in mitochondrial biogenesis, e.g., regulated by PPAR's receptors or PGC-1α coactivator, and (2) involved in neuronal or astroglial fate, during neural differentiation of hiPSC. The tested cell populations included hiPSC-derived neural stem cells (NSC), early neural progenitors (eNP), and neural progenitors (NP)...
October 13, 2018: Molecular Neurobiology
Lei Ma, Wen Niu, Jianrui Lv, Ji Jia, Miaozhang Zhu, Shuai Yang
Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1α is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10 ng/ml lipopolysaccharide (LPS) plus 10 U/ml interferon γ (IFNγ) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 µM AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), compared to the cells treated with LPS plus IFNγ only (P < 0...
October 12, 2018: Cellular and Molecular Neurobiology
Xiao-Hong Deng, Jing-Jing Liu, Xian-Jun Sun, Jing-Cheng Dong, Jian-Hua Huang
The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 μM significantly increased mitochondrial mass in HepG2 cells...
October 12, 2018: Acta Pharmacologica Sinica
Gabriele Civiletto, Sukru Anil Dogan, Raffaele Cerutti, Gigliola Fagiolari, Maurizio Moggio, Costanza Lamperti, Cristiane Benincá, Carlo Viscomi, Massimo Zeviani
The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, we show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse ( Cox15 sm / sm ). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15 sm / sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15 sm / sm mice...
October 11, 2018: EMBO Molecular Medicine
Mengistu Lemecha, Katsutaro Morino, Takeshi Imamura, Hirotaka Iwasaki, Natsuko Ohashi, Shogo Ida, Daisuke Sato, Osamu Sekine, Satoshi Ugi, Hiroshi Maegawa
Mitochondria are critical in heat generation in brown and beige adipocytes. Mitochondrial number and function are regulated in response to external stimuli, such as cold exposure and β3 adrenergic receptor agonist. However, the molecular mechanisms regulating mitochondrial biogenesis during browning, especially by microRNAs, remain unknown. We investigated the role of miR-494-3p in mitochondrial biogenesis during adipogenesis and browning. Intermittent mild cold exposure of mice induced PPARγ coactivator1-α (PGC1-α) and mitochondrial TFAM, PDH, and ANT1/2 expression along with uncoupling protein-1 (Ucp1) in inguinal white adipose tissue (iWAT)...
October 10, 2018: Scientific Reports
Monique Le Ret, Susan Belcher, Stefanie Graindorge, Clémentine Wallet, Sandrine Koechler, Mathieu Erhardt, Rosalind Williams-Carrier, Alice Barkan, José Manuel Gualberto
Thymidine kinase (TK) is a key enzyme of the salvage pathway that recycles thymidine nucleosides to produce dTTP. We identified the single TK of maize, denoted CPTK1, as an essential factor in the replication of the plastidial genome (cpDNA), demonstrating the essential function of the salvage pathway during chloroplast biogenesis. CPTK1 localizes to both plastids and mitochondria. Its absence results in an albino phenotype, reduced cpDNA copy number, and a severe deficiency for plastidial ribosomes. No significant effect was found on mitochondria, indicating that they are less reliant on the salvage pathway...
October 10, 2018: Plant Physiology
Zhibing Qiu, Xin Chen, Li Yin, Wen Chen, Yueyue Xu, Ben Jiang
Previous studies have shown that stomatin-like protein-2 (SLP-2) could regulate mitochondrial biogenesis and function. The study was designed to explore the contribution of SLP-2 to the myocardial ischemia and reperfusion (I/R) injury. Anesthetized rats were treated with SLP-2 and subjected to ischemia for 30 minutes before 3 hours of reperfusion. An oxygen-glucose deprivation/reoxygenation model of I/R was established in H9C2 cells. In vivo, SLP-2 significantly improved cardiac function recovery of myocardial I/R injury rats by increasing fractional shortening and ejection fraction...
October 10, 2018: Journal of Cellular Biochemistry
ChaoYuan Song, MaoYu Li, LinLin Xu, Yang Shen, Hui Yang, Mao Ding, XiangTian Liu, ZhaoHong Xie
Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease, but the pathogenesis is unclear. Damaged mitochondrial biogenesis has been observed in AD. Increasing evidence suggests that mitochondrial biogenesis is involved in the pathogenesis of AD, but the exact mechanism is unclear. In this study, we used the amyloid precursor protein Swedish mutations K594N/M595L (APPswe)/presenilin 1 with the exon-9 deletion (PS1dE9) transgenic mouse model of AD, which was successfully established by the expression of amyloid β precursor protein and presenilin 1 (PS1)...
October 9, 2018: Neuroreport
Richard G Lee, Danielle L Rudler, Oliver Rackham, Aleksandra Filipovska
Mitochondrial biogenesis is intimately dependent on the coordinated expression of the nuclear and mitochondrial genomes that is necessary for the assembly and function of the respiratory complexes to produce most of the energy required by cells. Although highly compacted in animals, the mitochondrial genome and its expression are essential for survival, development, and optimal energy production. The machinery that regulates gene expression within mitochondria is localised within the same compartment and, like in their ancestors, the bacteria, this machinery does not use membrane-based compartmentalisation to order the gene expression pathway...
October 8, 2018: Biochemical Society Transactions
Ehab A Ayaub, Karun Tandon, Manreet Padwal, Jewel Imani, Hemisha Patel, Anisha Dubey, Olivia Mekhael, Chandak Upagupta, Anmar Ayoub, Anna Dvorkin-Gheva, James Murphy, Philipp S Kolb, Sarka Lhotak, Jeffrey G Dickhout, Rick C Austin, Martin Rj Kolb, Carl D Richards, Kjetil Ask
Although recent evidence has shown that IL-6 is involved in enhanced alternative activation of macrophages toward a pro-fibrotic phenotype, the mechanisms leading to their increased secretory capacity are not fully understood. Here, we investigated the effect of IL-6 on endoplasmic reticulum (ER) expansion and alternative activation of macrophages in vitro. An essential mediator in this ER expansion process is the IRE1 pathway, which possesses a kinase and endoribonuclease domain to cleave XBP1 into a spliced bioactive molecule...
October 9, 2018: Immunology and Cell Biology
Hyoung Kyu Kim, Yun Gyeong Kang, Seung Hun Jeong, Nammi Park, Jubert Marquez, Kyung Soo Ko, Byoung Doo Rhee, Jung-Woog Shin, Jin Han
Unlike stable and immobile cell line conditions, animal hearts contract and relax to pump blood throughout the body. Mitochondria play an essential role by producing biological energy molecules to maintain heart function. In this study, we assessed the effect of heart mimetic cyclic stretch on mitochondria in a cardiac cell line. To mimic the geometric and biomechanical conditions surrounding cells in vivo, cyclic stretching was performed on HL-1 murine cardiomyocytes seeded onto an elastic micropatterned substrate (10% elongation, 0...
October 5, 2018: Biochemical and Biophysical Research Communications
Elisa Vilardo, Christa Nachbagauer, Aurélie Buzet, Andreas Taschner, Johann Holzmann, Walter Rossmanith
No abstract text is available yet for this article.
October 8, 2018: Nucleic Acids Research
Mahdi Vazirian, Seyed Mohammad Nabavi, Samineh Jafari, Azadeh Manayi
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme which monitors cellular energy status and regulates metabolism with energy balance. AMPK activation, as a master regulator of metabolism, plays role in key tissues like liver, skeletal muscles, and heart as well as central nervous system (CNS). Activation of the enzyme by indirect activators attracts scientific attentions to treat diabetes, obesity, cancer, and other related metabolic disorders like physiological and pathophysiological states in CNS...
October 2, 2018: Food and Chemical Toxicology
Omar M Khdour, Indrajit Bandyopadhyay, Nishant P Visavadiya, Sandipan Roy Chowdhury, Sidney M Hecht
Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease that is linked to transcriptional repression of the nuclear FXN gene encoding the essential mitochondrial protein frataxin (FXN). Compounds that increase frataxin levels may enable effective therapeutic intervention for blunting disease progression. Recently, we showed that lipophilic methylene violet (MV) and methylene blue (MB) analogues both conferred benefit to cultured FRDA cells in several regards, including ROS suppression, maintenance of mitochondrial membrane potential and increased ATP production...
September 1, 2018: MedChemComm
Mahendra Singh, Henry Denny, Christina Smith, Jorge Granados, Robert Renden
KEY POINTS: This study characterizes the mechanisms underlying defects in synaptic transmission when DRP1 is genetically eliminated. Viral-mediated knockout of DRP1 from the presynaptic terminal at the mouse calyx of Held increased initial release probability, reduced the size of synaptic vesicle recycling pool, and impaired synaptic vesicle recycling. Transmission defects could be partially restored by increasing intracellular calcium buffering capacity with EGTA-AM, implying close coupling of Ca2+ -channels to SVs was compromised...
October 4, 2018: Journal of Physiology
Natalie E Scholpa, Hannah Williams, Wenxue Wang, Daniel Corum, Aarti Narang, Stephen Tomlinson, Patrick G Sulllivan, Alexander G Rabchevsky, Rick G Schnellmann
A hallmark of the progressive cascade of damage referred to as secondary spinal cord injury (SCI) is vascular disruption resulting in decreased oxygen delivery and loss of mitochondria homeostasis. While therapeutics targeting restoration of single facets of mitochondrial function have proven largely ineffective clinically post-SCI, comprehensively addressing mitochondrial function via pharmacological stimulation of mitochondrial biogenesis (MB) is an underexplored strategy. This study examined the effects of formoterol, a mitochondrial biogenic FDA-approved selective and potent β<sub>2</sub>-adrenoreceptor (ADRB2) agonist, on recovery from SCI in mice...
October 3, 2018: Journal of Neurotrauma
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