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Mitochondrial respiration

Wangde Dai, Elissa Cheung, Rick J Alleman, Justin B Perry, Mitchell E Allen, David A Brown, Robert A Kloner
PURPOSE: Dysfunctional mitochondria are considered to be the major source of intracellular reactive oxygen species and play a central role in the pathophysiology of myocardial ischemia/reperfusion. This study sought to determine effects of mitochondria-targeted cytoprotective peptide SBT-20 on myocardial infarct size in two different models of ischemia/reperfusion. METHODS: For in vivo studies, anesthetized Sprague Dawley rats were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion...
October 17, 2016: Cardiovascular Drugs and Therapy
Jian-Jun Wen, Xianxiu Wan, John Thacker, Nisha Jain Garg
BACKGROUND: Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM. METHODS AND RESULTS: C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post-infection), treated with sildenafil (SIL, 1 mg/kg) twice per week for 3 weeks...
June 2016: JACC. Basic to Translational Science
Ivana Jochmanova, Karel Pacak
Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL)...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Trey K Sato, Mary Tremaine, Lucas S Parreiras, Alexander S Hebert, Kevin S Myers, Alan J Higbee, Maria Sardi, Sean J McIlwain, Irene M Ong, Rebecca J Breuer, Ragothaman Avanasi Narasimhan, Mick A McGee, Quinn Dickinson, Alex La Reau, Dan Xie, Mingyuan Tian, Jennifer L Reed, Yaoping Zhang, Joshua J Coon, Chris Todd Hittinger, Audrey P Gasch, Robert Landick
The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically...
October 2016: PLoS Genetics
Albert R Jones Iv, Tova Meshulam, Marcus F Oliveira, Nathan Burritt, Barbara E Corkey
BACKGROUND: Many tissues play an important role in metabolic homeostasis and the development of diabetes and obesity. We hypothesized that the circulating redox metabolome is a master metabolic regulatory system that impacts all organs and modulates reactive oxygen species (ROS) production, lipid peroxidation, energy production and changes in lipid turnover in many cells including adipocytes. METHODS: Differentiated human preadipocytes were exposed to the redox couples, lactate (L) and pyruvate (P), β-hydroxybutyrate (βOHB) and acetoacetate (Acoc), and the thiol-disulfides cysteine/ cystine (Cys/CySS) and GSH/GSSG for 1...
2016: PloS One
Takashi Owada, Hiroyuki Yamauchi, Shu-Ichi Saitoh, Shunsuke Miura, Hirofumi Machii, Yasuchika Takeishi
BACKGROUND: Senescence is a major factor that increases oxidative stress in mitochondria, which contributes toward the pathogenesis of heart disease. However, the effect of antioxidant therapy on cardiac mitochondria in aged-cardiac performance remains elusive. OBJECTIVES: We postulated that the mitochondrial targeting of superoxide scavenging would have benefits in the aged heart. METHODS AND RESULTS: Generation of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity increased in the heart of old mice compared with that in young mice...
October 12, 2016: Coronary Artery Disease
Md Abu Sayed, Yui Umekawa, Kikukatsu Ito
Skunk cabbage (Symplocarpus renifolius) blooms in early spring and its inflorescence, referred to as the spadix, can produce enough heat to melt snow. Here, we investigated glycolytic carbon flow at the PEP branch-point in thermogenic spadices. Our analyses revealed that petals and pistils in thermogenic florets exhibited higher expression of SrPEPC and SrAOX transcripts than those of SrPK, SrPEPCK, and SrPEPtase. Moreover, enzymatic analyses showed high activities of PEPC in the extracts from thermogenic florets...
October 14, 2016: Plant Signaling & Behavior
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms are unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD+/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
October 14, 2016: Journal of Neurochemistry
Vitaly K Koltover
There are two generally known concepts in biology of aging. Accordingly to the first one, there is a program of aging. The alternative concept advocates that aging proceeds stochastically. In this area of research, free radical-theory of aging, which was put forward by Denham Harman in fifties of XXth century, has determined the most heuristic line. The goal of this review is to demonstrate how the aging program and the aging stochastics are united on the basis of the systems theory of reliability. On this basis, universal features of aging, such as the exponential growth of mortality rate with time and correlation of longevity with the species-specific resting metabolism, are naturally explained...
October 9, 2016: Current Aging Science
Jonathan C Jun, Ronald Devera, Dileep Unnikrishnan, Mi-Kyung Shin, Shannon Bevans-Fonti, Qiaoling Yao, Aman Rathore, Haris Younas, Nils Halberg, Philipp E Scherer, Vsevolod Y Polotsky
: Hypoxia-inducible factor-1α (HIF-1α) in adipose tissue is known to promote obesity. We hypothesized that HIF-1α interferes with brown fat thermogenesis, thus decreasing energy expenditure. To test this hypothesis, we compared transgenic mice constitutively expressing HIF-1α in adipose tissues (HIF-1α++) at usual temperature (22 °C), where brown fat is somewhat active, or at thermoneutrality (30 °C), where brown fat is minimally active. HIF-1α++ mice or control litter mates were separated into room temperature (22 °C) or thermoneutrality (30 °C) groups...
October 14, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Xijun Liang, Lin Liu, Tingting Fu, Qian Zhou, Danxia Zhou, Liwei Xiao, Jing Liu, Yan Kong, Hui Xie, Fanchao Yi, Ling Lai, Rick B Vega, Daniel P Kelly, Steven R Smith, Zhenji Gan
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise in human muscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exercise-induced peroxisome proliferator-activated receptor-g coactivator 1α (PGC-1α)...
October 13, 2016: Journal of Biological Chemistry
Vishal R Mali, Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Jiang Xu, Xiao-Ping Yang, Suresh S Palaniyandi
Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7-11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts...
2016: PloS One
Bhabatosh Banik, Brett W Askins, Shanta Dhar
The field of intracellular organelle targeting using nanoparticle (NP) is mushrooming rapidly. Thus, the area of nanotechnology-enabled targeting of mitochondrion, the cellular powerhouse, for diseases characterized by mitochondrial dysfunctions such as cancer, diseases of the central nervous system, and cardiovascular diseases is also growing at a rapid pace. Optimization of a NP's ability to target the mitochondria requires quantification of the particles in this subcellular organelle and isolation of mitochondria from the cells...
October 13, 2016: Nanoscale
Judith Kandel, Alessia A Angelin, Douglas C Wallace, David M Eckmann
An abundance of research suggests that cellular mitochondrial and cytoskeletal disruption are related, but few studies have directly investigated causative connections between the two. We previously demonstrated that inhibiting microtubule and microfilament polymerization affects mitochondrial motility on the whole-cell level in fibroblasts. Since mitochondrial motility can be indicative of mitochondrial function, we now further characterize the effects of these cytoskeletal inhibitors on mitochondrial potential, morphology and respiration...
October 13, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Daniel Torralba, Francesc Baixauli, Francisco Sánchez-Madrid
Mitochondria regulate multiple cell processes, including calcium signaling, apoptosis and cell metabolism. Mitochondria contain their own circular genome encoding selected subunits of the oxidative phosphorylation complexes. Recent findings reveal that, in addition to being maternally inherited, mitochondria can traverse cell boundaries and thus be horizontally transferred between cells. Although, the physiological relevance of this phenomenon is still under debate, mitochondria uptake rescues mitochondrial respiration defects in recipient cells and regulates signaling, proliferation or chemotherapy resistance in vitro and in vivo...
2016: Frontiers in Cell and Developmental Biology
Marthe H R Ludtmann, Plamena R Angelova, Natalia N Ninkina, Sonia Gandhi, Vladimir L Buchman, Andrey Y Abramov
: Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Suriyan Ponnusamy, Quynh T Tran, Innocence Harvey, Heather S Smallwood, Thirumagal Thiyagarajan, Souvik Banerjee, Daniel L Johnson, James T Dalton, Ryan D Sullivan, Duane D Miller, Dave Bridges, Ramesh Narayanan
Most satiety-inducing obesity therapeutics, despite modest efficacy, have safety concerns that underscore the need for effective peripherally acting drugs. An attractive therapeutic approach for obesity is to optimize/maximize energy expenditure by increasing energy-utilizing thermogenic brown adipose tissue. We used in vivo and in vitro models to determine the role of estrogen receptor β (ER-β) and its ligands on adipose biology. RNA sequencing and metabolomics were used to determine the mechanism of action of ER-β and its ligands...
October 12, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Rekik A Muluye, Yuhong Bian, Li Wang, Paulos N Alemu, Huantian Cui, Xiaofei Peng, Shanshan Li
Background: Level of fatigue is related to the metabolic energy available to tissues and cells, mainly through mitochondrial respiration, as well fatigue is the most common symptom of poorly functioning mitochondria. Hence, dysfunction of these organelles may be the cause of the fatigue seen in Chronic fatigue (CF). Placenta has been used for treatment of fatigue and various disease, moreover peptides has known protect mitochondrial viability, and alleviate fatigue. These properties of placenta and peptides may link with its effect on mitochondria; therefore, it is highly important to investigate the effectiveness of placenta peptide on fatigue and mitochondrial dysfunction...
2016: Frontiers in Pharmacology
Anna Kicinska, Bartlomiej Augustynek, Bogusz Kulawiak, Wieslawa Jarmuszkiewicz, Adam Szewczyk, Piotr Bednarczyk
Potassium channels have been found in the inner mitochondrial membrane of various cells. These channels regulate the mitochondrial membrane potential, respiration and the production of reactive oxygen species. In this study, we identified the activity of a large-conductance Ca(2+)-regulated potassium channel (mitoBKCa channel) in mitoplasts isolated from a primary human dermal fibroblast cell line. A potassium selective current was recorded with a mean conductance of 280 ± 2 pS in a symmetrical 150 mM KCl solution...
October 11, 2016: Biochemical Journal
Marcelo Pedrosa Gomes, Fernanda Vieira da Silva Cruz, Elisa Monteze Bicalho, Felipe Viègas Borges, Marcia Bacelar Fonseca, Philippe Juneau, Queila Souza Garcia
Glyphosate-formulations are widely used in the Brazilian Cerrado (neotropical savanna) with little or no control, threatening population of the endangered species Dimorphandra wilsonii. We investigated the toxicity of different concentrations (0, 5, 25 and 50 mg l(-1)) of glyphosate acid and one of its formulations (Roundup(®)) on seed germination in D. wilsonii. Glyphosate acid and Roundup drastically decreased seed germination by decreasing seed respiration rates. The activation of antioxidant enzymes, ascorbate peroxidase and catalase assure no hydrogen peroxide accumulation in exposed seeds...
October 7, 2016: Environmental Pollution
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