Biology Commons^™

Sex-Associated Mitochondrial Genes: Tools For Understanding Unionid Reproduction And Development, Amy Louise Maynard

Graduate Theses/Dissertations

Gonochoristic species of the bivalve order Unionida possess two types of mitochondria. The female-inherited mitochondria (F-mt) is found in the somatic cells of both sexes, while male-inherited mitochondria (M-mt) is found in the male gonad. These mitochondria possess different open reading frames (M-ORF or F-ORF respectively). Previous studies suggested that two types of sperm might exist, each carrying one or the other mitochondrial haplotype, and it was hypothesized that the presence of either F-mt or M-mt in sperm may be involved in determination of offspring sex. I investigated this hypothesis in Bleedingtooth (Venustaconcha pleasii). Sperm samples were obtained from field-collected …

A Mitochondria-Anchored Isoform Of The Actin-Nucleating Spire Protein Regulates Mitochondrial Division, Uri Manor, Sadie Bartholomew, Gonen Golani, Eric Christenson, Michael Kozlov, Henry Higgs, James Spudich, Jennifer Lippincott-Schwartz

Dartmouth Scholarship

Mitochondrial division, essential for survival in mammals, is enhanced by an inter-organellar process involving ER tubules encircling and constricting mitochondria. The force for constriction is thought to involve actin polymerization by the ER-anchored isoform of the formin protein inverted formin 2 (INF2). Unknown is the mechanism triggering INF2-mediated actin polymerization at ER-mitochondria intersections. We show that a novel isoform of the formin-binding, actin-nucleating protein Spire, Spire1C, localizes to mitochondria and directly links mitochondria to the actin cytoskeleton and the ER. Spire1C binds INF2 and promotes actin assembly on mitochondrial surfaces. Disrupting either Spire1C actin- or formin-binding activities reduces mitochondrial constriction …

Physiological Performance Of Warm-Adapted Marine Ectotherms : Thermal Limits Of Mitochondrial Energy Transduction Efficiency., Eloy Martinez, Eric Hendricks, Michael Menze, Joseph Torres

Faculty and Staff Scholarship

Thermal regimes in aquatic systems have profound implications for the physiology of ectotherms. In particular, the effect of elevated temperatures on mitochondrial energy transduction (i.e. energy from carbon substrates to ATP) in tropical and subtropical teleosts may have profound consequences on organismal performance and population viability. Upper and lower whole-organism critical temperatures for teleosts suggest that subtropical and tropical species are not susceptible to the warming trends associated with climate change, but sub-lethal effects on energy transduction efficiency and population dynamics remain unclear. The goal of the present study was to compare the thermal sensitivity of processes associated with mitochondrial …

Loss Of Mitochondrial Dna Causes Decreased Cell Viability, Alan M. Herrera

Theses and Dissertations - UTB/UTPA

Mitochondria are an organellar network involved in cellular bioenergetics and apoptosis, and dynamically balance their organization between fusion and fission events. Mitochondrial DNA (mtDNA) and nuclear DNA combine to encode polypeptides for the complexes of oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. Loss of ΔΨm causes mitochondrial fission, which appears to be associated with the progression of apoptosis, a critical cell death mechanism that allows tissue homeostasis, developmental sculpturing, and the removal of unwanted cells. Using cultured human cell models of decreased ΔΨm (both genetic mtDNA-depleted ρ 0 and pharmacological …

Treatment Strategies That Enhance The Efficacy And Selectivity Of Mitochondria-Targeted Anticancer Agents, Josephine S. Modica-Napolitano, Volkmar Weissig

Biology Faculty Publications

Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including …

Triatominae (Hemiptera:Reduviidae) In Texas: Mitochondrial Genome Assembly, Trypanosoma Cruzi Detection, And Bacterial Community Analysis, Chissa-Louise Rivaldi

Biology Theses

The genus Triatoma contains vectors of the protozoan parasite Trypanosoma cruzi, the pathogen responsible for Chagas disease. The following research presents several inductive studies to develop vector control approaches targeted to the genus or species level. Two-hundred and eighty-two insects were collected, identified, and tested for the presence of T. cruzi. Four species of the Triatoma genus were collected - the overall incidence of T. cruzi was 52% (T. gerstaeckeri -51%, T. lecticularia – 92%, other, 29%). From these 282 insects, the bacterial communities of eight specimens of T. gerstaeckeri were sequenced and analyzed using pyrosequencing technology. The bacterial communities …

Changes In Gene Expression In Sirt3 Knockout Liver Cells, Randa Tao, Jamie Leclerc, Kübra Yildiz, Seong-Hoon Park, Barbara Jung, David Gius, Özkan Özden

Turkish Journal of Biology

The sirtuin (SIRT) gene family is reported to regulate critical intracellular processes from aging to cellular metabolism and repair. SIRT3 knockout (SIRT3-/-) mice develop receptor positive mammary tumors starting at 13 months and SIRT3 expression is decreased in human breast cancer samples as well as several other diseases. It is established that carcinogenesis results from the accumulation of multiple aberrant genetic events including the activation of oncogenes and inactivation of tumor-suppressor genes. To determine the potential early genomic events that may play a role in the tumor-permissive phenotype observed in SIRT3-/- cells, we compared gene expression profile in SIRT3-/- and …

Mitochondrial Dna-Related Disorders: Emphasis On Mechanisms And Heterogeneity, Umut Cagin, Jose Antonio Enriquez

Turkish Journal of Biology

Mitochondrial diseases are a heterogeneous group of disorders that are currently the focus of intense research. The many cell functions performed by mitochondria include ATP production, calcium homeostasis, and apoptosis. One of the unique properties of mitochondria is the existence of a separate mitochondrial genome (mitochondrial DNA, mtDNA) found in varying copy numbers and containing 37 genes, 13 of them encoding proteins. All 13 mitochondrially encoded proteins form part of oxidative phosphorylation complexes through combination with approximately 100 nuclear DNA-encoded proteins. Coregulation of nDNA and mtDNA is therefore essential for mitochondrial function, and this coregulation contributes to the heterogeneity and …

Melatonin, Mitochondria, And Ca2+ Homeostasis In The Exocrine Pancreas: An Overview, Antonio Gonzalez, Patricia Santofimia-Castaño, Gines Maria Salido

Turkish Journal of Biology

Melatonin, a derivative of the amino acid tryptophan, was initially thought to be mainly produced and secreted by the pineal gland; with time, it was also found in other tissues and organs, and even in plants. Since its discovery, the study of the role of the indole in cellular homeostasis has generated impressive data, which have led researchers to a common idea regarding the positive actions of melatonin in health. The uncontrolled production of free radicals in cellular systems leads to the situation termed oxidative stress, which has been signaled as the basis of disease and aging. In the exocrine …

Role Of Melatonin On Calcium Signaling And Mitochondrial Oxidativestress In Epilepsy: Focus On Trp Channels, Mustafa Naziroğlu

Turkish Journal of Biology

Calcium ion (Ca2+) accumulation and excessive oxidative stress in the hippocampus and brain cortex have long been known as major contributors to the etiology of epilepsy. I have reviewed the role of Ca2+ signaling through cation channels and mitochondria-mediated oxidative stress on epilepsy in human and animals. A review of the relevant papers and results from recent studies were obtained from PubMed and the Science Citation Index. Current literature findings indicate that melatonin and agomelatine reduce activation of hippocampal transient receptor potential (TRP), glutamate receptors, and voltage-gated calcium channels that are critical for the development of abnormal Ca2+ homeostasis and …

Melatonin As A Stabilizer Of Mitochondrial Function: Role In Diseases And Aging, Cristina Carrasco, Ana B. Rodriguez, Jose A. Pariente

Turkish Journal of Biology

It is now almost 60 years since the discovery of melatonin and new physiological functions of the indole continuously appear in the most recent studies worldwide. Experimental evidence emphasizes its importance as a stabilizer of the mitochondrial bioenergetics, which could be related to the prevention of development of aging and several diseases. In the next years, conscientious investigation about this topic should be undertaken by scientists of different research areas to achieve a better understanding of the molecular mechanisms implied. This will ultimately allow the development and clinical application of efficacious treatments.

Prooxidant Effects Of Melatonin: A Brief Review, Malwina S. Munik, Cem Ekmekçi̇oğlu

Turkish Journal of Biology

Melatonin acts classically through the widely expressed G protein-coupled membrane receptors MT1 and MT2, respectively. The functional role of the MT receptors is not fully clear with multiple effects, such as effects on the circadian, reproductive, immune, cardiovascular, and intestinal systems, being suggested. In addition to receptor-mediated effects, melatonin also acts as a potent antioxidant and it is quite evident that melatonin and its metabolites efficiently reduce oxidative damage to proteins, lipids, and DNA and also exert protective effects on mitochondria. The potent antioxidant activity of melatonin stems from various complex mechanisms, including direct scavenging of radicals, stimulation of antioxidant …

Mia40 Protein Serves As An Electron Sink In The Mia40-Erv1 Import Pathway, Sonya E. Neal, Deepa V. Dabir, Heather L. Tienson, Darryl M. Horn, Kathrin Glaeser, Rachel R. Ogozalek Loo, Antoni Barrientos, Carla M. Koehler

Biology Faculty Works

A redox-regulated import pathway consisting of Mia40 and Erv1 mediates the import of cysteine-rich proteins into the mitochondrial intermembrane space. Mia40 is the oxidoreductase that inserts two disulfide bonds into the substrate simultaneously. However, Mia40 has one redox-active cysteine pair, resulting in ambiguity about how Mia40 accepts numerous electrons during substrate oxidation. In this study, we have addressed the oxidation of Tim13 in vitro and in organello. Reductants such as glutathione and ascorbate inhibited both the oxidation of the substrate Tim13 in vitro and the import of Tim13 and Cmc1 into isolated mitochondria. In addition, a ternary complex consisting …

Ferric Reductases And Transporters That Contribute To Mitochondrial Iron Homeostasis, Anshika Jain

Theses and Dissertations

Iron (Fe) is the fourth most abundant element in the Earth’s crust, yet the availability of Fe to plants is often limited. This is because in most soil types, Fe precipitates as ferric-oxyhydroxy complexes, making it unavailable for uptake by plants. While the mechanisms involved in Fe uptake from the soil are relatively well understood, the mechanisms involved in its further distribution to the aerial portion of the plant and to subcellular compartments are not fully understood. During Fe deprivation, plants up-regulate root Fe acquisition machinery. How plants sense Fe deprivation and tie the Fe status of the plant to …

Evolution Of Ecological Dominance Of Yeast Species In High-Sugar Environments, Kathryn Marie Williams

Arts & Sciences Graduate Student Theses and Dissertations

Two challenging goals of evolutionary biology are to understand how evolutionary innovations evolve and how they contribute to the success of lineages. Evolutionary innovations may arise following whole genome duplication (WGD) events and they are suspected to contribute to the success of lineages by creating ecological opportunity. However, direct evidence for duplicated genes involved in evolutionary innovations remains rare, and the relationship between evolutionary innovations and the success of lineages may be very complex. In this study, I explore the relationship of evolutionary innovation, WGD, and the ecological dominance of yeast species in high-sugar environments. In budding yeast, a major …

Redox Proteomic Identification Of Hne-Bound Mitochondrial Proteins In Cardiac Tissues Reveals A Systemic Effect On Energy Metabolism After Doxorubicin Treatment, Y. Zhao, Sumitra Miriyala, L. Miao, Mihail I. Mitov, David M. Schnell, Sanjit Kumar Dhar, J. Cai, J. B. Klein, Rukhsana Sultana, D. Allan Butterfield, Mary Vore, I. Batinic-Haberle, Subbarao Bondada, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria after DOX treatment. A redox proteomics method involving two-dimensional electrophoresis followed by mass spectrometry and investigation of protein databases identified several HNE-modified mitochondrial proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the …

Metabolic Suppression In Mammalian Hibernation: The Role Of Mitochondria., James F Staples

Biology Publications

Hibernation evolved in some small mammals that live in cold environments, presumably to conserve energy when food supplies are low. Throughout the winter, hibernators cycle spontaneously between torpor, with low metabolism and near-freezing body temperatures, and euthermia, with high metabolism and body temperatures near 37°C. Understanding the mechanisms underlying this natural model of extreme metabolic plasticity is important for fundamental and applied science. During entrance into torpor, reductions in metabolic rate begin before body temperatures fall, even when thermogenesis is not active, suggesting active mechanisms of metabolic suppression, rather than passive thermal effects. Mitochondrial respiration is suppressed during torpor, especially …

Studies On Theraputic Potential Of Dichloroacetic Acid And Hene Laser In Cancer Treatment: Understanding The Mechanism Of Action, Zeiyad Nassaif Al-Karakooly

Theses and Dissertations

Cancer cells are often characterized by anaerobic glycolysis due to dysfunctional mitochondria that limits pyruvate uptake for aerobic respiration. Dichloroacetic acid (DCA), used in this study as a potential cancer treatment agent, targets mitochondria in cancer cells and is likely to correct mitochondrial dysfunction by resuming pyruvate uptake and therefore normal aerobic respiration. Our results suggest that DCA causes a significantly higher cytotoxicity in aggressive MCF-7 breast cancer cells than in non-aggressive MC3T3 osteoblastic cells. Apparently lower doses of DCA induce apoptosis whereas higher doses lead to non-specific cytotoxicity or necrosis. Increased cytotoxicity might be related to oxidative stress due …

Molecular Characterization Of The Freshwater Snail Physella Acuta, Journey R. Nolan

Biology ETDs

Current insights into general animal biology, including immune function, are derived mostly from a few model organisms, a necessity imposed by effort required for in-depth studies. Modern next-generation sequencing (NGS) enables genomics-level investigations to test whether specific aspects of biology are general or unique across animal phylogeny. Meaningful comparisons require thorough identification of phylogenetically-relevant species. To provide a touchstone for Biomphalaria glabrata, a freshwater snail that is a major study model for invertebrate immunity, physid snails (Physidae; Hygrophila; Panpulmonata; Gastropoda; Mollusca) will be developed as a model for comparative immunogenomics. Chapter 1 introduces current research capabilities and details the rationale …

Regulation Of Succinate-Fuelled Mitochondrial Respiration In Liver And Skeletal Muscle Of Hibernating Thirteen-Lined Ground Squirrels., Jason C L Brown, Dillon J Chung, Alex N Cooper, James F Staples

Biology Publications

Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during …

Mitochondrial Genome Evolution In Pupillid Land Snails, Jason D. Marquardt

Biology ETDs

Pupillid land snails (Family Pupillidae) are small (< 6mm) snails with a broad geographic distribution and often found in very high density in their habitat. The sequencing of the mitochondrial genome (mt genome) of three pupillid taxa has been undertaken to understand their genome evolution more fully. The Gastrocopta cristata mitochondrial genome is 14,060 bp in length and contains 13 protein coding genes, 2 rRNA genes and 22 tRNA genes. The Pupilla muscorum, and Vertigo pusilla genomes contain all of the same genes but are of differing total sizes, 14,149 bp and 14,078 bp respectively. The AT content of the three genomes is similar at ~71% A+T which is comparable to their closest sequenced relatives. There are no major gene rearrangements among the mt genomes of the three pupillids, but the positions of many tRNA genes differ from those of Albinaria caerulea. There is a genomic sequence region of high concentration of thymine on the leading strand of the mt genome that is shared among all three genomes as well as their relatives.

Mitochondrial Glutathione Transport: Implications For Bcl-2 And Neuronal Survival, Heather Marie Wilkins

Electronic Theses and Dissertations

Oxidative stress is a contributing factor to many neurodegenerative diseases. In particular, mitochondria are a key source of oxidative stress due to electron leakage at the level of the electron transport chain. To combat the endogenous production of reactive oxygen and reactive nitrogen species mitochondria are equipped with several redox-cycling systems, such as glutathione (GSH). Mitochondrial GSH has been shown to be a critical reservoir of this antioxidant, where selective depletion of mitochondrial GSH can induce apoptosis in several systems. Many studies have intricately linked Bcl-2 to cellular GSH status and it has been previously shown that Bcl-2 is a …

Metabolism Of Brain Cortex And Cardiac Muscle Mitochondria In Hibernating 13-Lined Ground Squirrels Ictidomys Tridecemlineatus., Kirsten Gallagher, James F Staples

Biology Publications

During bouts of torpor, mitochondrial metabolism is known to be suppressed in the liver and skeletal muscle of hibernating mammals. This suppression is rapidly reversed during interbout euthermic (IBE) phases, when whole-animal metabolic rate and body temperature (T(b)) return spontaneously to euthermic levels. Such mitochondrial suppression may contribute significantly to energy savings, but the capacity of other tissues to suppress mitochondrial metabolism remains unclear. In this study we compared the metabolism of mitochondria from brain cortex and left ventricular cardiac muscle between animals sampled while torpid (stable T(b) near 5°C) and in IBE (stable T(b) near 37°C). Instead of isolating …

Reconstruction Of Family-Level Phylogenetic Relationships Within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes, Malcolm Hill, April L. Hill, Et. Al.

Biology Faculty Publications

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges.

Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosa^p, Myxospongiae …

An Investigation Of Alternative Oxidase Presence, Expression, And Regulation In The Moss Physcomitrella Patens, Karina I. Neimanis

Theses and Dissertations (Comprehensive)

Alternative oxidase (AOX) is an inner mitochondrial membrane protein that introduces a branch point at ubiquinone within the respiratory electron transport system (ETS). The AOX protein bypasses two sites of proton translocation within the ETS and as a result the yield of ATP per oxygen consumed is significantly reduced. Although AOX appears to be energetically wasteful, recent studies have revealed that AOX has a wide taxonomic distribution. AOX multigene families, transcripts, protein levels, and enzymatic activity have been most thoroughly characterized in many angiosperm (flowering) plants. Given the data available for angiosperm AOXs, evidence of non-angiosperm AOXs in the primary …

Hepatopancreas Mitochondria Of Mytilus Galloprovincialis: Effect Of Zinc Ions On Mitochondrial Bioenergetics And Metabolism, Antonino De Lisi, Ermelinda Prato, Francesca Biandolino, Giulio Sarli, Donatella Negro, Gianluigi La Piana, Domenico Marzulli

Turkish Journal of Biology

Oxygen uptake, respiratory complexes, and metabolic activities have been studied in mitochondria isolated from the hepatopancreata of Mytilus galloprovincialis collected in the “Mar Grande” of Taranto (Ionian Sea, Italy). Although exposure to 5.0 µg Zn^{2+}/L resulted in a significant increase of states 3 and 4 respiration with glutamate + pyruvate as respiratory substrate, it was found that the exposure of mussels to different concentrations of Zn^{2+} (2.5–7.5 µg/L) neither inhibited mitochondrial respiration nor exerted any inhibitory effect on representative mitochondrial dehydrogenases. It rather stimulates these activities, producing an extra synthesis of adenosine triphosphate by hepatopancreas mitochondria and possibly increasing its …

Treatment Of Aortic Heart Valve Conduit With Glutamine And Heat Shock As A Means To Deter The Constituent Cellular Population From Becoming Apoptotic, Alyce Marie Linthurst Jones

Theses and Dissertations in Biomedical Sciences

Cryopreserved allograft heart valves represent the best solution for a patient with a failing heart valve. However, the constituent cells become apoptotic and within months of transplant the heart valve becomes acellular and the recipient's cells do not repopulate the allograft (3, 51). A strategy to prevent this situation would be to minimize or prevent apoptosis from occurring by strategically altering steps during heart valve processing. Recently it has been demonstrated that: 1) Heat shock protein 70 is a negative modulator of the apoptotic cascade; 2) Cells in culture exposed to hypothermic conditions produce heat shock protein 70 upon rewarming; …

Macroevolutionary Dynamics And Historical Biogeography Of Primate Diversification Inferred From A Species Supermatrix, Christopher A. Emerling, Mark S. Springer, Robert W. Meredith, John Gatesy, Jong Park, Daniel L. Rabosky, Tanja Stadler, Cynthia Steiner, Oliver A. Ryder, Jan E. JanecˇKa, Colleen A. Fisher, William J. Murphy

Biology

Phylogenetic relationships, divergence times, and patterns of biogeographic descent among primate species are both complex and contentious. Here, we generate a robust molecular phylogeny for 70 primate genera and 367 primate species based on a concatenation of 69 nuclear gene segments and ten mitochondrial gene sequences, most of which were extracted from GenBank. Relaxed clock analyses of divergence times with 14 fossil-calibrated nodes suggest that living Primates last shared a common ancestor 71–63 Ma, and that divergences within both Strepsirrhini and Haplorhini are entirely post-Cretaceous. These results are consistent with the hypothesis that the Cretaceous-Paleogene mass extinction of non-avian dinosaurs …

Causes And Consequences Of Mitochondrial Variation In Caenorhabditid Nematodes, Kiley Ann Hicks

Dissertations and Theses

Mitochondria are dynamic organelles that harbor their own stream-lined genome and generate much of the ATP necessary to sustain eukaryotic life via an electron transport chain (ETC). Because of the central role for mitochondria in organismal physiology, mitochondrial genetic and phenotypic variation can alter organismal fitness and affect population genetic and evolutionary outcomes. Despite the far-reaching relevance of mitochondria to evolutionary processes and human health, we lack a basic understanding of the causes and consequences of mitochondrial genetic and phenotypic variation. In this thesis, I quantified mitochondrial reactive oxygen species (ROS), membrane potential (δΨM), and mitochondrial morphological traits within Caenorhabditis …

Truncation Of The Mrp20 Protein Reveals New Ribosome‐Assembly Subcomplex In Mitochondria, Jasvinder Kaur, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

Mitochondrial ribosomal protein 20 (Mrp20) is a component of the yeast mitochondrial large (54S) ribosomal subunit and is homologous to the bacterial L23 protein, located at the ribosomal tunnel exit site. The carboxy‐terminal mitochondrial‐specific domain of Mrp20 was found to have a crucial role in the assembly of the ribosomes. A new, membrane‐bound, ribosomal‐assembly subcomplex composed of known tunnel‐exit‐site proteins, an uncharacterized ribosomal protein, MrpL25, and the mitochondrial peroxiredoxin (Prx), Prx1, accumulates in an mrp20ΔC yeast mutant. Finally, data supporting the idea that the inner mitochondrial membrane acts as a platform for the ribosome assembly process are discussed.