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Liver mitochondria

Dan Wei, Ningning Zheng, Lanyan Zheng, Leting Wang, Liang Song, Luning Sun
Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action. Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg• d) and a SBP-treated group (SBP, 100 mg/kg• d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed...
2018: Frontiers in Pharmacology
Hana Kimura, Kohei Arasaki, Yuki Ohsaki, Toyoshi Fujimoto, Takayuki Ohtomo, Junji Yamada, Mitsuo Tagaya
Lipid droplets (LDs) are ubiquitous organelles that contain neutral lipids and are surrounded by a phospholipid monolayer. How proteins specifically localize to the phospholipid monolayer of the LD surface has been a matter of extensive investigations. In the present study we show that syntaxin 17 (Stx17), a SNARE protein whose expression in the liver is regulated by diet, participates in LD biogenesis by regulating the distribution of acyl-CoA synthetase 3 (ACSL3), a key enzyme for LD biogenesis that redistributes from the endoplasmic reticulum to LDs during LD formation...
March 16, 2018: Journal of Lipid Research
Xianxun Shi, Huiyuan Bai, Ming Zhao, Xiaorong Li, Xianchao Sun, Hongbo Jiang, Ailing Fu
Drug-induced liver injury shares a common feature of mitochondrial dysfunction. Mitochondrial therapy (mitotherapy), which replaces malfunctional mitochondria with functional exogenous mitochondria, may be a fundamental approach for treating drug-mediated hepatotoxicity. Here, we suggested that mitochondria isolated from human hepatoma cell could be used to treat acetaminophen (APAP)-induced liver injury in mice. When the mitochondria were added into the cell media, they could enter primarily cultured mouse hepatocyte...
March 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Luke MacMillan, Garrett Tingley, Sara K Young, Kathy A Clow, Edward W Randell, Margaret E Brosnan, John T Brosnan
Background: Formate is produced in mitochondria via the catabolism of serine, glycine, dimethylglycine, and sarcosine. Formate produced by mitochondria may be incorporated into the cytosolic folate pool where it can be used for important biosynthetic reactions. Previous studies from our lab have shown that cobalamin deficiency results in increased plasma formate concentrations. Objective: Our goal was to determine the basis for elevated formate in vitamin B-12 deficiency...
March 1, 2018: Journal of Nutrition
Lilian Cristina Pereira, Murilo Pazin, Mariana Furio Franco-Bernardes, Airton da Cunha Martins, Gustavo Rafael Mazzaron Barcelos, Márcio Cesar Pereira, João Paulo Mesquita, Jairo Lisboa Rodrigues, Fernando Barbosa, Daniel Junqueira Dorta
Nanotechnology is a growing branch of science that deals with the development of structural features bearing at least one dimension in the nano range. More specifically, nanomaterials are defined as objects with dimensions that range from 1 to 100 nm, which give rise to interesting properties. In particular, silver and titanium nanoparticles (AgNPs and TiNPs, respectively) are known for their biological and biomedical properties and are often used in consumer products such as cosmetics, food additives, kitchen utensils, and toys...
May 2018: Journal of Trace Elements in Medicine and Biology
Ursula J Lemberger, Claudia D Fuchs, Christian Schöfer, Andrea Bileck, Christopher Gerner, Tatjana Stojakovic, Makoto M Taketo, Michael Trauner, Gerda Egger, Christoph H Österreicher
Background: Wnt/β-catenin signaling plays a crucial role in embryogenesis, tissue homeostasis, metabolism and malignant transformation of different organs including the liver. Continuous β-catenin signaling due to somatic mutations in exon 3 of the Ctnnb1 gene is associated with different liver diseases including cancer and cholestasis. Results: Expression of a degradation resistant form of β-catenin in hepatocytes resulted in 100% mortality within 31 days after birth...
February 16, 2018: Oncotarget
A C Van Erp, R A Rebolledo, D Hoeksma, N R Jespersen, P J Ottens, R Nørregaard, M Pedersen, C Laustsen, J G M Burgerhof, J C Wolters, J Ciapaite, H E Bøtker, H G D Leuvenink, B Jespersen
Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted)...
March 13, 2018: Scientific Reports
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
Jennifer Rieusset
The contact sites that the endoplasmic reticulum (ER) forms with mitochondria, called mitochondria-associated membranes (MAMs), are a hot topic in biological research, and both their molecular determinants and their numerous roles in several signaling pathways are is continuously evolving. MAMs allow the exchange between both organelles of lipids, calcium (Ca2+ ), and likely reactive oxygen species, allowing adaptations of both cellular bioenergetics and cell fate depending of cellular needs or stresses. Therefore, it is not surprising that MAMs affect cellular metabolism...
March 9, 2018: Cell Death & Disease
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, François Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea E Bochem, Kees G Hovingh, Edward B Thorp, Emmanuel L Gautier, Dagmar Kratky, Paul A Da Silva-Jardine, Laurent Yvan-Charvet
<u>Rationale:</u> Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. <u>Objective:</u> Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. <u>Methods and Results:</u> We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC...
March 9, 2018: Circulation Research
Daniel Elbaum, Maria G Beconi, Edith Monteagudo, Annalise Di Marco, Maria S Quinton, Kathryn A Lyons, Andrew Vaino, Steven Harper
In cells, phosphorylation of pantothenic acid to generate phosphopantothenic acid by the pantothenate kinase enzymes is the first step in coenzyme A synthesis. Pantothenate kinase 2, the isoform localized in neuronal cell mitochondria, is dysfunctional in patients with pantothenate kinase-associated neurodegeneration. Fosmetpantotenate is a phosphopantothenic acid prodrug in clinical development for treatment of pantothenate kinase-associated neurodegeneration, which aims to replenish phosphopantothenic acid in patients...
2018: PloS One
Russell P Goodman, Sarah Calvo, Vamsi K Mootha
Compartmentalization is a fundamental design principle of eukaryotic metabolism.  Here, we review the compartmentalization of NAD+/NADH and NADP+/NADPH with a focus on the liver, an organ that experiences the extremes of biochemical physiology each day.  Historical studies of the liver, using classical biochemical  measurements of redox-coupled metabolites, have given rise to the view that mitochondrial NAD(H) pools tend to be oxidized and important for energy homeostasis, whereas cytosolic NADP(H) pools tend to be highly reduced for reductive biosynthesis...
March 7, 2018: Journal of Biological Chemistry
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
José Teixeira, Catarina Oliveira, Fernando Cagide, Ricardo Amorim, Jorge Garrido, Fernanda Borges, Paulo J Oliveira
Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN3 ) based on the dietary antioxidant gallic acid was developed. AntiOxBEN3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN3 showed also limited toxicity on human hepatocarcinoma cells...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Simona Ioja, Srikanth Singamsetty, Catherine Corey, Lanping Guo, Faraaz Shah, Michael J Jurczak, Bryan J McVerry, Sruti Shiva, Christopher P O'Donnell
Although acute exposure to hypoxia can disrupt metabolism, longer-term exposure may normalize glucose homeostasis or even improve glucose disposal in the presence of obesity. We examined the effects of two-week exposure to room air (Air), continuous 10% oxygen (C10%), and 12 hr nocturnal periods of 10% oxygen (N10%) on glucose disposal, insulin responsiveness, and mitochondrial function in lean and obese C57BL/6J mice. Both C10% and N10% improved glucose disposal relative to Air in lean and obese mice without evidence of an increase in insulin responsiveness; however, only the metabolic improvements with N10% exposure occurred in the absence of confounding effects of weight loss...
2018: Oxidative Medicine and Cellular Longevity
Daihyun Kim, Jinghui Luo, Edgar A Arriaga, Alexandra Ros
Resolving the heterogeneity of particle populations by size is important when the particle size is a signature of abnormal biological properties leading to disease. Accessing size heterogeneity in the sub-micrometer regime is particularly important to resolve populations of sub-cellular species or diagnostically relevant bioparticles. Here, we demonstrate a ratchet migration mechanism capable of separating sub-µm sized species by size and apply it to biological particles. The phenomenon is based on a deterministic ratchet effect, is realized in a microfluidic device and exhibits fast migration allowing separation in tens of seconds...
March 6, 2018: Analytical Chemistry
Nidhi Kuksal, Danielle Gardiner, Dake Qi, Ryan J Mailloux
Recent work has found that complex I is the sole source of reactive oxygen species (ROS) during myocardial ischemia-reperfusion (IR) injury. However, it has also been reported that heart mitochondria can also generate ROS from other sources in the respiratory chain and Krebs cycle. This study examined the impact of partial complex I deficiency due to selective loss of the Ndufs4 gene on IR injury to heart tissue. Mice heterozygous for NDUFS4 (NDUFS4+/-) did not display any significant changes in overall body or organ weight when compared to wild-type (WT) littermates...
March 1, 2018: Biochemical and Biophysical Research Communications
Yohei Tatematsu, Haruhi Fujita, Hiroki Hayashi, Atsushi Yamamoto, Atsushi Tabata, Hideaki Nagamune, Kazuto Ohkura
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and pain. In the present study, we examined the effects of celecoxib, a cyclooxygenase-2 (COX-2)-selective NSAID, on rat liver mitochondrial function. Celecoxib dose-dependently induced mitochondria swelling, which was not suppressed by cyclosporine A (CsA). The oxygen consumption rate in mitochondria-suspended solution was facilitated by the addition of celecoxib, and its uncoupling activity was observed. Celecoxib also suppressed SF6847-induced uncoupling, and appeared to exert inhibitory effects on the electron transport chain...
2018: Biological & Pharmaceutical Bulletin
Edwin R Price, Tushar S Sirsat, Sarah K G Sirsat, Thomas Curran, Barney J Venables, Edward M Dzialowski
The 'membrane pacemaker' hypothesis proposes a biochemical explanation for among-species variation in resting metabolism, based on the positive correlation between membrane docosahexaenoic acid (DHA) and metabolic rate. We tested this hypothesis using a novel model, altricial red-winged blackbird nestlings, predicting that the proportion of DHA in muscle and liver membranes should increase with the increasing metabolic rate of the nestling as it develops endothermy. We also used a dietary manipulation, supplementing the natural diet with fish oil (high DHA) or sunflower oil (high linoleic acid) to alter membrane composition and then assessed metabolic rate...
February 27, 2018: Journal of Experimental Biology
Jun Song, Sai-Jun Ma, Jian-Hua Luo, Hui Zhang, Ri-Xiong Wang, Hui Liu, Li Li, Zhi-Guang Zhang, Rui-Xiang Zhou
Globally, gastric cancer (GC) is one of the most common types of cancer and the third leading cause of cancer‑related death. In China, gastric and liver cancers have the highest mortality rates. Melatonin, also known as N-acetyl‑5-methoxytryptamine, is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness. Melatonin has been shown to inhibit various carcinomas, including GC. There are many different hypotheses to explain the anticancer effects of melatonin, including stimulation of apoptosis, inhibition of cell growth, regulation of anticancer immunity, induction of free-radical scavenging, and the competitive inhibition of estrogen...
February 26, 2018: Oncology Reports
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