Biochemistry Commons^™

Down The Iron Path: Mitochondrial Iron Homeostasis And Beyond, Jonathan Dietz, Jennifer L. Fox, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the …

A Multi-Approach And Multi-Scale Platform To Model Cd4+ T Cells Responding To Infections, Kenneth Y. Wertheim, Bhanwar Lal Puniya, Alyssa La Fleur, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. …

Development Of High Value Oil Traits Using The Model Oilseed Crop Camelina Sativa, Evan Updike

Department of Biochemistry: Dissertations, Theses, and Student Research

Plant oils are an important source of food, fuel, and feed in our society today. The oil found in the seeds of plants is composed almost entirely of triacylglycerol (TAG) molecules, which consist of three fatty acids esterified to a glycerol backbone. As crude oil supplies decline, vegetable oils are gaining traction as a renewable substitute to petroleum-based materials in fuels, lubricants, and specialty oleochemicals. However, as it currently stands vegetable oils do not possess the properties necessary to fill the void of a petroleum free world.

To address this problem, plant biotechnologists have done extensive work on genetic engineering …

Characterization Of Sphingolipid Biosynthesis And Modification In Plants, Dongdong Zhang

Department of Biochemistry: Dissertations, Theses, and Student Research

Sphingolipids are ubiquitous membrane lipids in eukaryotic cells. Ceramides, the backbone of sphingolipids, are synthesized by ceramide synthases (CerSs), which form amide bonds between long-chain bases (LCBs) and the acyl groups of acyl-CoAs. Class I CerS works predominantly towards C16-CoA, whereas Class II CerS works towards C24-CoA. Plant sphingolipids generally have 16-carbon and 24-carbon as the major acyl groups. However, the sphingolipids of Oryza sativa and Zea mays have 20-carbon and 24-carbon as the predominant acyl groups. This dissertation aims to understand the substrate preference of CerSs in monocots such as rice. Phylogenetic analysis shows the Class I CerSs from …

Toward Sustainable Production Of Value-Added Bioenergy And Industrial Oils In Oilseed And Biomass Feedstocks, Kiyoul Park, Sanju A. Sanjaya, Truyen Quach, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Plant fatty acids are used for food, feed, fuel, and industrial materials. Structurally and chemically diverse fatty acids, referred to as unusual or specialized fatty acids, are found in the seed oils of diverse plant species. Many unusual fatty acids have potential use as alternative and renewable sources of biofuels and bio-based industrial feedstocks due to their variant structures' physical or functional properties. Oils enriched in these fatty acids can increase the value of oilseed crops and provide co-products that can be readily extracted from lignocellulosic materials in biomass crops. Here, we describe recent progress on strategies for enhancement of …

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding Rna Targets, Challenges And Therapeutic Opportunities, Xinghui Sun, Mark W. Feinberg

Department of Biochemistry: Faculty Publications

Cellular senescence is a stable form of cell cycle arrest in response to various stressors. While it serves as an endogenous pro-resolving mechanism, detrimental effects ensue when it is dysregulated. In this review, we introduce recent advances for cellular senescence and inflammaging, the underlying mechanisms for the reduction of nicotinamide adenine dinucleotide in tissues during aging, new knowledge learned from p16 reporter mice, and the development of machine learning algorithms in cellular senescence. We focus on pathobiological insights underlying cellular senescence of the vascular endothelium, a critical interface between blood and all tissues. Common causes and hallmarks of endothelial senescence …

Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …

Multi-Strategy Engineering Greatly Enhances Provitamin A Carotenoid Accumulation And Stability In Arabidopsis Seeds, Tianhu Sun, Qinlong Zhu, Ziqing Wei, Lauren A. Owens, Tara Fish, Hyojin Kim, Theodore W. Thannhauser, Edgar B. Cahoon, Li Li

Department of Biochemistry: Faculty Publications

Staple grains with low levels of provitamin A carotenoids contribute to the global prevalence of vitamin A deficiency and therefore are the main targets for provitamin A biofortification. However, carotenoid stability during both seed maturation and postharvest storage is a serious concern for the full benefits of carotenoid biofortified grains. In this study, we utilized Arabidopsis as a model to establish carotenoid biofortification strategies in seeds. We discovered that manipulation of carotenoid biosynthetic activity by seed-specific expression of Phytoene synthase (PSY) increases both provitamin A and total carotenoid levels but the increased carotenoids are prone to degradation during …

Integrative Computational Approach Identifies Drug Targets In Cd4+ T-Cell-Mediated Immune Disorders, Bhanwar L. Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

CD4⁺ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immunerelated diseases. CD4⁺ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4⁺ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico …

Studies Of The Dutpase Of The Western Corn Rootworm, Carlos A. Riera-Ruiz

School of Biological Sciences: Dissertations, Theses, and Student Research

The western corn rootworm (WCR), Diabrotica virgifera virgifera, is a major corn pest in the United States and Europe. WCR has developed resistance to multiple management strategies, including Cry proteins. Even though the biology and ecology have been thoroughly studied in WCR, their genome and molecular mechanisms are understudied. This work focuses on the ubiquitous enzyme deoxyuridine triphosphatase (dUTPase) encoded by the DUT gene. dUTPase hydrolyzes dUTP into dUMP and pyrophosphate. It contributes to genome stability by keeping the uracil-to-thymine ratio at a certain level. In WCR, two dUTPase isoforms were predicted using transcriptome analyses. These two potential isoforms …

Europium Sulfide Nanoprobes Predict Antiretroviral Drug Delivery Into Hiv-1 Cell And Tissue Reservoirs, Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Joellyn Mcmillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya

Department of Biochemistry: Faculty Publications

Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify …

Crispr/Cas9-Induced Fad2 And Rod1 Mutations Stacked With Fae1 Confer High Oleic Acid Seed Oil In Pennycress (Thlaspi Arvense L.), Brice A. Jarvis, Trevor B. Romsdahl, Michaela G. Mcginn, Tara J. Nazarenus, Edgar B. Cahoon, Kent D. Chapman, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Pennycress (Thlaspi arvense L.) is being domesticated as an oilseed cash cover crop to be grown in the off-season throughout temperate regions of the world. With its diploid genome and ease of directed mutagenesis using molecular approaches, pennycress seed oil composition can be rapidly tailored for a plethora of food, feed, oleochemical and fuel uses. Here, we utilized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology to produce knockout mutations in the FATTY ACID DESATURASE2 (FAD2) and REDUCED OLEATE DESATURATION1 (ROD1) genes to increase oleic acid content. High oleic acid (18:1) oil is valued for its oxidative stability that is …

Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Wastewater biosolids are a promising feedstock for production of value-added renewable chemicals. Methane-producing archaea (methanogens) are already used to produce renewable biogas via the anaerobic treatment of wastewater. The ability of methanogens to efficiently convert dissolved organic carbon into methane makes them an appealing potential platform for biorefining using metabolic engineering. We have engineered a strain of the methanogen Methanosarcina acetivorans to produce the volatile hemiterpene isoprene in addition to methane. The engineered strain was adapted to grow in municipal wastewater through cultivation in a synthetic wastewater medium. When introduced to municipal wastewater the engineered methanogens were able to compete …

Isoprene Production From Municipal Wastewater Biosolids By Engineered Archaeon Methanosarcina Acetivorans, Sean Carr, Jared Aldridge, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Wastewater biosolids are a promising feedstock for production of value-added renewable chemicals. Methane-producing archaea (methanogens) are already used to produce renewable biogas via the anaerobic treatment of wastewater. The ability of methanogens to efficiently convert dissolved organic carbon into methane makes them an appealing potential platform for biorefining using metabolic engineering. We have engineered a strain of the methanogen Methanosarcina acetivorans to produce the volatile hemiterpene isoprene in addition to methane. The engineered strain was adapted to grow in municipal wastewater through cultivation in a synthetic wastewater medium. When introduced to municipal wastewater the engineered methanogens were able to compete …

Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud

Department of Biochemistry: Faculty Publications

The bacterium Clostridium perfringens causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell–cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Targeted binding of CpE to specific claudins, encoded by its C-terminal domain (cCpE), loosens TJ barriers to trigger molecular leaks between cells. Cytotoxicity results from claudin-bound CpE complexes forming pores in cell membranes. In mammalian tissues, ∼24 claudins govern TJ barriers—but the basis for …

Highlighting Membrane Protein Structure And Function: A Celebration Of The Protein Data Bank, Fei Li, Pascal F. Egea, Alex J. Vecchio, Ignacio Asial, Meghna Gupta, Joana Paulino, Ruchika Bajaj, Miles Sasha Dickinson, Shelagh Fergunson-Miller, Brian C. Monk, Robert M. Stroud

Department of Biochemistry: Faculty Publications

Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Many biological processes are carried out by proteins embedded in or associated with such membranes. Determination of membrane protein (MP) structures at atomic or near-atomic resolution plays a vital role in elucidating their structural and functional impact in biology. This endeavor has determined 1198 unique MP structures as of early 2021. The value of these structures is expanded greatly by deposition of their three-dimensional (3D) coordinates into the Protein Data Bank (PDB) after the first atomic MP structure was elucidated in 1985. Since …

A Co-Opted Steroid Synthesis Gene, Maintained In Sorghum But Not Maize, Is Associated With A Divergence In Leaf Wax Chemistry, Lucas Busta, Elizabeth Schmitz, Dylan K. Kosma, James Schnable, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Virtually all land plants are coated in a cuticle, a waxy polyester that prevents nonstomatal water loss and is important for heat and drought tolerance. Here, we describe a likely genetic basis for a divergence in cuticular wax chemistry between Sorghum bicolor, a drought tolerant crop widely cultivated in hot climates, and its close relative Zea mays (maize). Combining chemical analyses, heterologous expression, and comparative genomics, we reveal that: 1) sorghum and maize leaf waxes are similar at the juvenile stage but, after the juvenile-to-adult transition, sorghum leaf waxes are rich in triterpenoids that are absent from maize; 2) …

Engineering Src Homology 2 Domains With Improved Specificity For Sulfotyrosine, Anya Morozov

Honors Program: Senior Projects (Public)

Protein tyrosine O-sulfation (PTS) is a common post-translational modification that has been implicated in a variety of biological processes and human illnesses. Despite continued progress in the field of sulfoproteomics, the extent and function of sulfated tyrosine (sulfotyrosine) residues is a topic of ongoing research. Previous work in the Guo Lab has identified Src Homology-2 (SH2) mutants that have a high affinity for sulfotyrosine along with retained high affinity for their natural ligand, phosphorylated tyrosine (phosphotyrosine). In this thesis, I attempted to generate SH2 mutants that have high affinity and specificity for sulfotyrosine over phosphotyrosine. While I successfully generated …

Using Crispr-Cas9 To Construct Knockout Mutants In Dna-Repair Genes In Arabidopsis Thaliana, David Campbell

Honors Program: Senior Projects (Public)

The mitochondria are known as the powerhouse of the cell, and just like a real powerhouse, it can be a dangerous place to store sensitive information. Energy generation and redox reactions in the mitochondria can cause damage to the DNA stored there, resulting in a higher mutation rate. Compared to their animal counterparts, however, plant mitochondria exhibit a lower mutation rate and a higher recombination rate. It is hypothesized that the unique DNA repair methods present in plant mitochondria are responsible for the phenomena observed there. To study the mechanics of DNA-repair in this organelle, however, researchers must be able …

Structural Basis For Clostridium Perfringens Enterotoxin Targeting Of Claudins At Tight Junctions In Mammalian Gut, Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud

Department of Biochemistry: Faculty Publications

The bacterium Clostridium perfringens causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell–cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Targeted binding of CpE to specific claudins, encoded by its C-terminal domain (cCpE), loosens TJ barriers to trigger molecular leaks between cells. Cytotoxicity results from claudin-bound CpE complexes forming pores in cell membranes. In mammalian tissues, 24 claudins govern TJ barriers—but the basis for …

Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio Ponte Viana, Roman M. Levytskyy, Ruchika Anand, Andreas S. Reichert, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required …

Generating Pennycress (Thlaspi Arvense) Seed Triacylglycerols And Acetyl-Triacylglycerols Containing Medium-Chain Fatty Acids, Maliheh Esfahanian, Tara J. Nazarenus, Meghan M. Freund, Gary Mcintosh, Winthrop B. Phippen, Mary E. Phippen, Timothy P. Durrett, Edgar B. Cahoon, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Thlaspi arvense L. (pennycress) is a cold-tolerant Brassicaceae that produces large amounts of seeds rich in triacylglycerols and protein, making it an attractive target for domestication into an offseason oilseed cash cover crop. Pennycress is easily genetically transformed, enabling synthetic biology approaches to tailor oil properties for specific biofuel and industrial applications. To test the feasibility in pennycress of producing TAGs and acetyl-TAGs rich in medium-chain fatty acids (MCFAs; C6–C14) for industrial, biojet fuel and improved biodiesel applications, we generated transgenic lines with seed-specific expression of unique acyltransferase (LPAT and diacylglycerol acyltransferase) genes and thioesterase (FatB) genes isolated from Cuphea …

Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …

Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun

Department of Biochemistry: Faculty Publications

Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …

Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta

Department of Biochemistry: Faculty Publications

Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv. Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as …

Integrative Network Analyses Of Transcriptomics Data Reveal Potential Drug Targets For Acute Radiation Syndrome, Robert Moore, Bhanwar Lal Puniya, Robert Powers, Chittibabu Guda, Kenneth W. Bayles, David Berkowitz, Tomas Helikar

Department of Biochemistry: Faculty Publications

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene co-expression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, …

Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta

Department of Biochemistry: Faculty Publications

Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv. Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as …

Lysosomal Slc46a3 Modulates Hepatic Cytosolic Copper Homeostasis, Jung-Hwan Kim, Tsutomu Matsubara, Jaekwom Lee, Cristina Fenollar-Ferrer, Kyungreem Han, Donghwan Kim, Shang Jia, Christopher J. Chang, Heejung Yang, Tomokazu Nagano, Kristopher W. Krausz, Sun Hee Yim, Frank J. Gonzalez

Department of Biochemistry: Faculty Publications

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function. SLC46A3 was localized to the lysosome where it modulated intracellular copper levels. Forced expression of hepatic SLC46A3 resulted in decreased mitochondrial membrane potential and abnormal mitochondria morphology consistent with lower copper levels. SLC46A3 expression increased hepatic lipid accumulation similar to the known effects of TCDD exposure in mice and humans. The TCDD-induced hepatic triglyceride accumulation was significantly …

Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun

Department of Biochemistry: Faculty Publications

Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …

Teaching Metabolism In Upper-Division Undergraduate Biochemistry Courses Using Online Computational Systems And Dynamical Models Improves Student Performance, Christine S. Booth, Changsoo Song, Michelle E. Howell, Achilles Rasquinha, Aleš Saska, Resa M. Helikar, Sharmin M. Sikich, Brain A. Couch, Karin Van Dijk, Rebecca Roston, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Understanding metabolic function requires knowledge of the dynamics, interdependence, and regulation of metabolic networks. However, multiple professional societies have recognized that most undergraduate biochemistry students acquire only a surface-level understanding of metabolism. We hypothesized that guiding students through interactive computer simulations of metabolic systems would increase their ability to recognize how individual interactions between components affect the behavior of a system under different conditions. The computer simulations were designed with an interactive activity (i.e., module) that used the predict–observe–explain model of instruction to guide students through a process in which they iteratively predict outcomes, test their predictions, modify the interactions …