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Mitochondria cell differentiation

Maximilian E Müller, Sofia Vikstrom, Maria König, Rita Schlichting, Christiane Zarfl, Christian Zwiener, Beate I Escher
Some environmental pollutants impair mitochondria, which are of vital importance as energy factories in eukaryotic cells. Mitochondrial toxicity was quantified by measuring the change of the oxygen consumption rate (OCR) of HepG2 cells with the Agilent Seahorse XFe96 Analyzer. Various mechanisms of mitochondrial toxicity, including inhibition of the electron transport chain or the ATP-synthase as well as uncoupling of oxidative phosphorylation, were differentiated by dosing the sample in parallel with reference compounds following the OCR over time...
February 19, 2019: Environmental Toxicology and Chemistry
Celia Salazar, Alvaro A Elorza, Glenda Cofre, Paula Ruiz-Hincapie, Orian Shirihai, Lina María Ruiz
HIG2A promotes cell survival under hypoxia and mediates the assembly of complex III and complex IV into respiratory chain supercomplexes. In the present study, we show that human HIGD2A and mouse Higd2a gene expressions are regulated by hypoxia, glucose, and the cell cycle-related transcription factor E2F1. The latter was found to bind the promoter region of HIGD2A. Differential expression of the HIGD2A gene was found in C57BL/6 mice in relation to tissue and age. Besides, the silencing of HIGD2A evidenced the modulation of mitochondrial dynamics proteins namely, OPA1 as a fusion protein increases, while FIS1, a fission protein, decreases...
February 18, 2019: Journal of Cellular Physiology
Olivier Reelfs, Vincenzo Abbate, Agostino Cilibrizzi, Mark A Pook, Robert C Hider, Charareh Pourzand
Mitochondrial labile iron (LI) is a major contributor to the susceptibility of skin fibroblasts to ultraviolet A (UVA)-induced oxidative damage leading to necrotic cell death via ATP depletion. Mitochondria iron overload is a key feature of the neurodegenerative disease Friedreich's ataxia (FRDA). Here we show that cultured primary skin fibroblasts from FRDA patients are 4 to 10-fold more sensitive to UVA-induced death than their healthy counterparts. We demonstrate that FRDA cells display higher levels of mitochondrial LI (up to 6-fold on average compared to healthy counterparts) and show higher increase in mitochondrial reactive oxygen species (ROS) generation after UVA irradiation (up to 2-fold on average), consistent with their differential sensitivity to UVA...
February 19, 2019: Metallomics: Integrated Biometal Science
Yosuke Tabei, Hiroko Fukui, Ayako Nishioka, Yuji Hagiwara, Kei Sato, Tadashi Yoneda, Tamami Koyama, Masanori Horie
Multi walled carbon nanotubes (MWCNTs) are one of the most intensively explored nanomaterials because of their unique physical and chemical properties. Due to the widespread use of MWCNTs, it is important to investigate their effects on human health. The precise mechanism of MWCNT toxicity has not been fully elucidated. The present study was designed to examine the mechanisms of MWCNT toxicity toward human promyelocytic leukemia HL-60 cells. First, we found that MWCNTs decreased the viability of neutrophil-like differentiated HL-60 cells but not undifferentiated HL-60 cells...
February 18, 2019: Scientific Reports
Hsiu-Chi Ting, Li-Tzu Chen, Jo-Yu Chen, Yi-Li Huang, Rui-Cheng Xin, Jui-Fen Chan, Yuan-Hao Howard Hsu
BACKGROUND: Supplemented fatty acids can incorporate into cardiolipin (CL) and affect its remodeling. The change in CL species may alter the mitochondrial membrane composition, potentially disturbing the mitochondrial structure and function during inflammation. METHOD: To investigate the effect of the unsaturation of fatty acids on CL, we supplemented macrophage-like RAW264.7 cells with 18-carbon unsaturated fatty acids including oleic acid (OA, 18:1), linoleic acid (LA, 18:2), α-linolenic acid (ALA, 18:3), γ-linolenic acid (GLA, 18:3), and stearidonic acid (SDA, 18:4)...
February 14, 2019: Lipids in Health and Disease
Ekaterina S Kharechkina, Anna B Nikiforova, Vera V Teplova, Irina V Odinokova, Olga V Krestinina, Yulia L Baburina, Svetlana A Kruglova, Alexey G Kruglov
BACKGROUND: The opening of the permeability transition pore (PTP) in mitochondria plays a critical role in the pathogenesis of numerous diseases. Mitochondrial matrix pyridine nucleotides are potent regulators of the PTP, but the role of extramitochondrial nucleotides is unclear. METHODS: The PTP opening was explored in isolated mitochondria and mitochondria in permeabilized differentiated and undifferentiated cells in the presence of added NAD(P)(H) in combination with Mg2+ , adenine nucleotides (AN), and the inhibitors of AN translocase (ANT), voltage-dependent anion channel (VDAC), and cyclophilin D...
February 11, 2019: Biochimica et biophysica acta. General subjects
Amanda K Jones, Laura D Brown, Paul J Rozance, Natalie J Serkova, William W Hay, Jacob E Friedman, Stephanie R Wesolowski
Intrauterine growth restricted (IUGR) fetal sheep have increased hepatic glucose production (HGP) that is resistant to suppression during a hyperinsulinemic-isoglycemic clamp (insulin-clamp). We hypothesized that the IUGR fetal liver would have activation of metabolic and signaling pathways that support HGP and inhibition of insulin signaling pathways. To test this, we used transcriptomic profiling with liver samples from control (CON) and IUGR fetuses receiving saline or an insulin-clamp. The IUGR liver had upregulation of genes associated with gluconeogenesis/glycolysis, transcription factor regulation, and cytokine responses and downregulation of genes associated with cholesterol synthesis, amino acid degradation, and detoxification pathways...
February 13, 2019: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Tao Wang, Jiao Zhang, Min Hu, Yuehui Zhang, Peng Cui, Xin Li, Juan Li, Edvin Vestin, Mats Brännström, Linus R Shao, Håkan Billig
The underlying mechanisms of polycystic ovarian syndrome (PCOS)-induced endometrial dysfunction are not fully understood, and although accumulating evidence shows that the use of metformin has beneficial effects in PCOS patients, the precise regulatory mechanisms of metformin on endometrial function under PCOS conditions have only been partially explored. To address these clinical challenges, this study aimed to assess the protein expression patterns of glycolytic enzymes, estrogen receptor (ER), and androgen receptor (AR) along with differences in mitochondria-dependent apoptosis in PCOS patients with and without endometrial hyperplasia in vivo and to investigate the effects of metformin in PCOS patients with endometrial hyperplasia in vitro ...
2019: International Journal of Biological Sciences
Yanhan Dong, Wenhua Xu, Cuiyun Liu, Peijun Liu, Peifeng Li, Kun Wang
Reactive oxygen species (ROS) are a class of reactive molecules that have been implicated in a variety of cardiovascular diseases, accompanied by disorder of multiple signaling events. As cardiomyocytes maintain abundant of mitochondria, which supply the major source of endogenous ROS, oxidative damage to mitochondria often drives apoptotic cell death and initiates cardiac pathology. In recent years, non-coding RNAs (ncRNAs) have received much attention to uncover their roles in regulating gene expression during those pathological events in the heart, such as myocardial infarction, cardiac hypertrophy, and heart failure...
2019: International Journal of Biological Sciences
Mark A Lampert, Amabel M Orogo, Rita H Najor, Babette C Hammerling, Leonardo J Leon, Bingyan J Wang, Taeyong Kim, Mark A Sussman, Åsa B Gustafsson
Cell-based therapies represent a very promising strategy to repair and regenerate the injured heart to prevent progression to heart failure. To date, these therapies have had limited success due to a lack of survival and retention of the infused cells. Therefore, it is important to increase our understanding of the biology of these cells and utilize this information to enhance their survival and function in the injured heart. Mitochondria are critical for progenitor cell function and survival. Here, we demonstrate the importance of mitochondrial autophagy, or mitophagy, in the differentiation process in adult cardiac progenitor cells (CPCs)...
February 11, 2019: Autophagy
Zi-Xian Liu, Fang Dong, Sen Zhang, Ming-Zhe Han, Hideo Ema
Mitochondria are double-membrane organelles existing only in eukaryotic cells. Mitochondria perform various important functions,such as producing energy,regulating signal transduction,and contributing to stress response. Recent studies have highlighted an important role of mitochondria in the determination of hematopoietic stem cells (HSC) fate. Limited biogenesis or timely clearance of mitochondria is an important way against oxidative stress,which favors the quiescence of HSC. Accumulation of mitochondria may lead to proliferation of HSC,even the aging of HSC...
February 2019: Zhongguo Shi Yan Xue Ye Xue za Zhi
William D McCaig, Matthew A Deragon, Robert J Haluska, Alexa L Hodges, Payal S Patel, Timothy J LaRocca
In this protocol we detail a method to obtain subcellular fractions of U937 cells without the use of ultracentrifugation or indiscriminate detergents. This method utilizes hypotonic buffers, digitonin, mechanical lysis and differential centrifugation to isolate the cytoplasm, mitochondria and plasma membrane. The process can be scaled to accommodate the needs of researchers, is inexpensive and straightforward. This method will allow researchers to determine protein localization in cells without specialized centrifuges and without the use of commercial kits, both of which can be prohibitively expensive...
January 18, 2019: Journal of Visualized Experiments: JoVE
Carlos Sanz-Garcia, Kyle L Poulsen, Damien Bellos, Han Wang, Megan R McMullen, Xiaoxia Li, Saurabh Chattopadhyay, Ganes Sen, Laura E Nagy
BACKGROUND & AIMS: Interferon regulatory factor 3 (IRF3) is a transcription factor mediating anti-viral responses, yet recent evidence indicates that IRF3 also has critical non-transcriptional functions, including activating RIG-I-like receptors-induced IRF-3-mediated pathway of apoptosis (RIPA) and restricting activity of NFκB. Using a novel murine model expressing only non-transcriptional IRF3 activity (Irf3S1/S1 ), we tested the hypothesis that non-transcriptional functions of IRF3 modulate innate immune responses in the Gao-binge (acute on chronic) model of alcohol-related liver disease...
January 30, 2019: Journal of Hepatology
Sebastian Yu, Cheng-Che E Lan, Hsin-Su Yu
Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low-level laser light (coherent light) or light-emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes...
February 2019: Experimental Dermatology
Xuexian Fang, Hao Wang, Dan Han, Enjun Xie, Xiang Yang, Jiayu Wei, Shanshan Gu, Feng Gao, Nali Zhu, Xiangju Yin, Qi Cheng, Pan Zhang, Wei Dai, Jinghai Chen, Fuquan Yang, Huang-Tian Yang, Andreas Linkermann, Wei Gu, Junxia Min, Fudi Wang
Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3 -/- , Mlkl -/- , or Fadd -/- Mlkl -/- mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death...
January 28, 2019: Proceedings of the National Academy of Sciences of the United States of America
Ji-Eun Park, Yoon-Jae Kim, Seung Gee Lee, Ji Young Kim, Jin-Yong Chung, Seon-Yong Jeong, Hyongjong Koh, Jeanho Yun, Hwan Tae Park, Young Hyun Yoo, Jong-Min Kim
The initial steps of steroidogenesis occur in the mitochondria. Dynamic changes in the mitochondria are associated with their fission and fusion. Therefore, understanding the cellular and molecular relationship between steroidogenesis and mitochondrial dynamics is important. The hypothesis of the present study is that mitochondrial fission and fusion are closely associated with steroid hormone synthesis in the testicular Leydig cells. Steroid hormone production, induced by dibutyryl cyclic-adenosine monophosphate (dbcAMP) in Leydig cells, was accompanied by increased mitochondrial mass...
January 25, 2019: Endocrinology
Chin-Wen Wei, Tyng-An Zhou, Ivan L Dzhagalov, Chia-Lin Hsu
T cells utilize different metabolic programs to match their functional needs during differentiation and proliferation. Mitochondria are crucial cellular components responsible for supplying cell energy; however, excess mitochondria also produce reactive oxygen species (ROS) that could cause cell death. Therefore, the number of mitochondria must constantly be adjusted to fit the needs of the cells. This dynamic regulation is achieved in part through the function of lysosomes that remove surplus/damaged organelles and macromolecules...
January 9, 2019: Journal of Visualized Experiments: JoVE
Hanan B Elajaili, Laura Hernandez-Lagunas, Kalina Ranguelova, Sergey Dikalov, Eva Nozik-Grayck
The accurate and specific detection of reactive oxygen species (ROS) in different cellular and tissue compartments is essential to the study of redox-regulated signaling in biological settings. Electron paramagnetic resonance spectroscopy (EPR) is the only direct method to assess free radicals unambiguously. Its advantage is that it detects physiologic levels of specific species with a high specificity, but it does require specialized technology, careful sample preparation, and appropriate controls to ensure accurate interpretation of the data...
January 11, 2019: Journal of Visualized Experiments: JoVE
Claire L Carter, Kim G Hankey, Catherine Booth, Gregory L Tudor, George A Parker, Jace W Jones, Ann M Farese, Thomas J MacVittie, Maureen A Kane
The acute radiation syndrome of the gastrointestinal tract has been histologically characterized, but the molecular and functional mechanisms that lead to these cellular alterations remain enigmatic. Mass spectrometry imaging is the only technique that enables the simultaneous detection and cellular or regional localization of hundreds of biomolecules in a single experiment. This current study utilized matrix-assisted laser desorption/ionization mass spectrometry imaging for the molecular characterization of the first natural history study of gastrointestinal acute radiation syndrome in the nonhuman primate...
January 23, 2019: Health Physics
Maria Troullinaki, Vasileia-Ismini Alexaki, Ioannis Mitroulis, Anke Witt, Anne Klotzsche-von Ameln, Kyoung-Jin Chung, Triantafyllos Chavakis, Matina Economopoulou
The mechanism underlying vasoproliferative retinopathies like retinopathy of prematurity (ROP) is hypoxia-triggered neovascularisation. Nerve growth factor (NGF), a neurotrophin supporting survival and differentiation of neuronal cells may also regulate endothelial cell functions. Here we studied the role of NGF in pathological retinal angiogenesis in the course of the ROP mouse model. Topical application of NGF enhanced while intraocular injections of anti-NGF neutralizing antibody reduced pathological retinal vascularization in mice subjected to the ROP model...
January 24, 2019: Journal of Cellular and Molecular Medicine
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