Life Sciences Commons^™

Identification Of The Binding Partners For Hspb2 And Cryab Reveals Myofibril And Mitochondrial Protein Interactions And Non-Redundant Roles For Small Heat Shock Proteins, Kelsey Murphey Langston

Theses and Dissertations

Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity. As such, mutations in this family of proteins result in a wide variety of diseases from cancers to cardiomyopathies. The sHSPs Beta-2 (HspB2) and alpha-beta crystalline (CryAB) are two of the ten human sHSPs and are both expressed in cardiac and skeletal muscle cells. A heart that cannot properly recover or defend against stressors such as extreme heat or cold, oxidative/reductive stress, and heavy metal-induced stress will constantly struggle to maintain efficient function. Accordingly, CryAB is required …

Metabolic Remodeling And Mitochondrial Dysfunction In Maladaptive Right Ventricular Hypertrophy Secondary To Pulmonary Arterial Hypertension, Jose Gomez-Arroyo

Theses and Dissertations

Right ventricular dysfunction is the most frequent cause of death in patients with pulmonary arterial hypertension. Although abnormal energy substrate use has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in failing right ventricular tissue remain incomplete. In the present dissertation we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. Two different rat models of RV hypertrophy were studied. The model of right ventricular failure (SU5416/hypoxia) exhibited a significantly decreased gene expression of peroxisome proliferator-activated receptor- coactivator-1α, peroxisome proliferator- activated receptor-α and estrogen-related receptor-α. The …

Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams

Dartmouth Scholarship

Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …

Modulation Of Bax/Bak Dependent Apoptosis By Sirtuin 3 And Mitochondrial Permeability Transition By Sirtuin 4, Manish Verma

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondria are dynamic organelles that regulate a myriad of cellular functions, including energy production and metabolic regulation. Mitochondria are also a critical regulator of cell death signaling cascades modulating both apoptotic and necrotic cell death. However, what determines which cell death pathway is activated is still unclear. The mitochondrial/intrinsic pathway of apoptosis is dependent on the activation of pro-apoptotic proteins, Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). Once the integrity of outer mitochondrial membrane (OMM) is compromised, pro-apoptotic intermembrane space proteins like cytochrome c, Smac/Diablo, Omi/HtrA2 and AIF are released into the cytoplasm, which activates the post-mitochondrial …

Are Long Chain Acyl Coas Responsible For Suppression Of Mitochondrial Metabolism In Hibernating 13-Lined Ground Squirrels?, Alex Cooper

Electronic Thesis and Dissertation Repository

I found 44% suppression of succinate-fuelled liver mitochondrial respiration in torpid 13-lined ground squirrels compared to interbout euthermia (IBE). Palmitoyl CoA, predicted to suppress respiration by inhibiting succinate transport at the dicarboxylate transporter (DCT), reduced respiration by ~70%, while butylmalonate, a known inhibitor of the DCT, only inhibited respiration by ~40%. In both cases inhibition of respiration proportionally affected both torpid and IBE mitochondria, suggesting that the DCT is likely not already inhibited in torpid mitochondria. The addition of carnitine, predicted to reverse suppression by facilitating transport of palmitoyl CoA into the mitochondrial matrix, had no rescuing effect on the …

A Detergent-Free Strategy For The Reconstitution Of Active Enzyme Complexes From Native Biological Membranes Into Nanoscale Discs, Ashley R. Long, Catherine C. O’Brien, Ketan Malhotra, Christine T. Schwall, Arlene D. Albert, Nathan N. Alder

Open Access Author Fund Awardees' Articles

Background

The reconstitution of membrane proteins and complexes into nanoscale lipid bilayer structures has contributed significantly to biochemical and biophysical analyses. Current methods for performing such reconstitutions entail an initial detergent-mediated step to solubilize and isolate membrane proteins. Exposure to detergents, however, can destabilize many membrane proteins and result in a loss of function. Amphipathic copolymers have recently been used to stabilize membrane proteins and complexes following suitable detergent extraction. However, the ability of these copolymers to extract proteins directly from native lipid bilayers for subsequent reconstitution and characterization has not been explored.

Results

The styrene-maleic acid (SMA) copolymer effectively …

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 Genomes Of Two Barklice, Psococerastis Albimaculata And Longivalvus Hyalospilus (Psocoptera: Psocomorpha): Contrasting Rates In Mitochondrial Gene Rearrangement Between Major Lineages Of Psocodea, Hu Li, Renfu Shao, Fan Song, Xuguo Zhou, Qianqian Yang, Zhihong Li, Wanzhi Cai

Entomology Faculty Publications

The superorder Psocodea has ∼10,000 described species in two orders: Psocoptera (barklice and booklice) and Phthiraptera (parasitic lice). One booklouse, Liposcelis bostrychophila and six species of parasitic lice have been sequenced for complete mitochondrial (mt) genomes; these seven species have the most rearranged mt genomes seen in insects. The mt genome of a barklouse, lepidopsocid sp., has also been sequenced and is much less rearranged than those of the booklouse and the parasitic lice. To further understand mt gene rearrangements in the Psocodea, we sequenced the mt genomes of two barklice, Psococerastis albimaculata and Longivalvus hyalospilus, the first representatives from …

Intrinsic Apoptotic Pathway: Effects Of Calcium On Murine Cytochrome C Release In Brain And Liver Mitochondria, Dane M. Edwards

Senior Honors Theses

A cell may use one of three main apoptotic pathways leading to programmed cell death: the extrinsic pathway, the perforin/granzyme pathway and the intrinsic pathway. The most pertinent to this discussion is the intrinsic pathway, which utilizes the mitochondria as an essential intermediary. Mitochondria’s primary function in relation to this pathway is the subsequent release of pro-apoptotic factors including cytochrome c, which activate a caspase cascade leading to the death of the cell. Cytochrome c is released partly due to an increase in cytosolic calcium levels. Two methods of the release of cytochrome c have been proposed. The first is …

Integrated Analysis Of Cytochrome P450 Gene Superfamily In The Red Flour Beetle, Tribolium Castaneum, Fang Zhu, Timothy W. Moural, Kapil Shah, Subba Reddy Palli

Entomology Faculty Publications

BACKGROUND: The functional and evolutionary diversification of insect cytochrome P450s (CYPs) shaped the success of insects. CYPs constitute one of the largest and oldest gene superfamilies that are found in virtually all aerobic organisms. Because of the availability of whole genome sequence and well functioning RNA interference (RNAi), the red flour beetle, Tribolium castaneum serves as an ideal insect model for conducting functional genomics studies. Although several T. castaneum CYPs had been functionally investigated in our previous studies, the roles of the majority of CYPs remain largely unknown. Here, we comprehensively analyzed the phylogenetic relationship of all T. castaneum CYPs …

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 …

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 …

Reconstruction Of Family-Level Phylogenetic Relationships Within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes, Malcolm S. Hill, April L. Hill, Jose V. Lopez, Kevin J. Peterson, Shirley Pomponi, Maria C. Diaz, Robert W. Thacker, Maja Adamska, Nicole Boury-Esnault, Paco Cárdenas, Andia Chaves-Fonnegra, Elizabeth Danka, Bre-Onna De Laine, Dawn Formica, Eduardo Hajdu, Gisele Lobo-Hajdu, Sarah Klontz, Christine C. Morrow, Jignasa Patel, Bernard Picton, Davide Pisani, Deborah Pohlmann, Niamh E. Redmond, John Reed, Stacy Richey, Ana Riesgo, Ewelina Rubin, Zach Russell, Klaus Rützler, Erik A. Sperling, Michael Di Stefano, James E. Tarver, Allen G. Collins

Marine & Environmental Sciences Faculty Articles

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, …

Biochemical Aspects Of The Thermal Sensitivity And Energy Balance Of Polar, Tropical And Subtropical Teleosts, Eloy Martinez

USF Tampa Graduate Theses and Dissertations

The maintenance of a functional energy balance in ectothermic fauna could be challenging in a thermally disparate environment. Biochemical adaptations at the enzyme and membrane levels allows for a set compensatory mechanism that allow the individual to maintain an energetic surplus, thus allocating energy for growth and reproduction. The present work describes how the energetic machinery in the cell, particularly the mitochondrion, could be affected by temperature changes. More specifically, this work aimed to determine how environmental temperature affects the mitochondria energetic performance of fishes from disparate thermal regimes.

Mitochondrial ATP production efficiency was evaluated in fishes from polar, tropical …

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 …