Life Sciences Commons^™

Mitochondrial Dynamics And Respiration Within Cells With Increased Open Pore Cytoskeletal Meshes, David H. Jang, Sarah C. Seeger, Martha E. Grady, Frances S. Shofer, David M. Eckmann

Mechanical Engineering Faculty Publications

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and …

Mechanism Of Transcription Anti-Termination In Human Mitochondria., Hauke S Hillen, Andrey V Parshin, Karen Agaronyan, Yaroslav I Morozov, James J Graber, Aleksandar Chernev, Kathrin Schwinghammer, Henning Urlaub, Michael Anikin, Patrick Cramer, Dmitry Temiakov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp," providing high processivity to the EC. …

Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose …

Defining The Immune Response And Cellular Pathologies In Multiple System Atrophy, Annamarie Valenti

Masters Theses

Multiple System Atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (α-Syn) in oligodendrocytes of the central nervous system (CNS). A previous study in our lab used Affymetrix DNA microarray analysis to show the downregulation of various mitochondrial related genes, as well as the upregulation of genes involved in inflammatory/immune responses in MSA brain tissue. Therefore, it is hypothesized that an increased presence of immune proteins exists in the MSA brain accompanied by glial cell pathology including decreases in cell metabolism and cell viability. This study uses immunohistochemistry (IHC) to show the increased presence of CD68 …

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as …

Temperature Induces Significant Changes In Both Glycolytic Reserve And Mitochondrial Spare Respiratory Capacity In Colorectal Cancer Cell Lines, Mihail I. Mitov, Jennifer W. Harris, Michael Alstott, Yekaterina Y. Zaytseva, B. Mark Evers, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach.

This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32°C, 37°C and 42°C using assay …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Electronic Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures

Arts & Sciences Electronic Theses and Dissertations

The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …

Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Publications and Research

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …

Effect Of Trehalose As An Additive To Dimethyl Sulfoxide Solutions On Ice Formation, Cellular Viability, And Metabolism., Jason Solocinski, Quinn Osgood, Mian Wang, Aaron Connolly, Michael A. Menze, Nilay Chakraborty

Faculty Scholarship

Cryopreservation is the only established method for long-term preservation of cells and cellular material. This technique involves preservation of cells and cellular components in the presence of cryoprotective agents (CPAs) at liquid nitrogen temperatures (−196 °C). The organic solvent dimethyl sulfoxide (Me₂SO) is one of the most commonly utilized CPAs and has been used with various levels of success depending on the type of cells. In recent years, to improve cryogenic outcomes, the non-reducing disaccharide trehalose has been used as an additive to Me₂SO-based freezing solutions. Trehalose is a naturally occurring non-toxic compound found in bacteria, …

The Prohibitin Protein Complex Promotes Mitochondrial Stabilization And Cell Survival In Hematologic Malignancies, Elisa Robles Escajeda

Open Access Theses & Dissertations

Lymphocyte proliferation and differentiation is coordinated with high precision in healthy humans and is vital to maintaining a normal immune system. Imbalance of these events can result in the development of autoimmune diseases, immunodeficiencies and hematopoietic malignancies. These pathologies, specifically leukemia and lymphoma have a high incidence of relapse and mortality due to limited treatment options. Therefore, there is a critical need to characterize the signal transduction pathways and understand molecular hallmarks that mediate T cell activation in order to develop new strategies for diagnosis and treatments of these diseases.

Prohibitins (PHB1 and PHB2) have been proposed to play important …

Reproductive Competency And Mitochondrial Variation In Aged Syrian Hamster Oocytes, Fang Li, Frank J. Castora, Wentia Ford, Khalid Alarid, Howard W. Jones Jr., R. James Swanson

Biological Sciences Faculty Publications

The hamster is a useful model of human reproductive biology because its oocytes are similar to those in humans in terms of size and structural stability. In the present study we evaluated fecundity rate, ovarian follicular numbers, ova production, mitochondrial number, structure and function, and cytoplasmic lamellae (CL) in young (2–4 months) and old (12–18 months) Syrian hamsters (Mesocricetus auratus). Young hamsters had higher fertilisation rates and larger litters than old hamsters (100 vs 50% and 9.3 +/- 0.6 vs 5.5 +/- 0.6, respectively). Ovarian tissue from superovulated animals showed a 46% decrease in preantral follicles in old …