Biology Commons^™

Nadh Flim Reveals Cellular Bioenergetics And Mitochondrial Morphology During Drosophila Convergent Extension, Maria Espana Pena

Graduate Theses and Dissertations

Mitochondria are dynamic organelles that can fragment or fuse to support different bioenergetic demands and cellular processes, although the role of mitochondrial fission and fusion during embryonic development is not well understood. Fluorescence lifetime imaging (FLIM) of the mitochondrial cofactor NADH can be used to visualize mitochondrial networks and infer aspects of cellular bioenergetics in a label-free manner. We used NADH FLIM to test whether germband cells undergo changes in cellular metabolism during Drosophila convergent extension (CE)––a process in which hundreds of epithelial cells undergo coordinated intercalation to elongate the embryo. Contrary to our expectations, we did not observe significant …

Mitochondria Dynamics In Microglia During Health, Inflammation, And Aging, Alicia Nicole Pietramale

Dartmouth College Ph.D Dissertations

Microglia continually surveil the brain, allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to tissue homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, and phagocytic engulfment in the intact brain has remained unclear. In this dissertation, I combine intravital imaging, ultrastructural analyses, and metabolic and cytoskeletal markers to investigate how mitochondrial organization relates to microglial function across health, inflammation, and aging.

I first show that microglial processes diverge in their mitochondrial content, with some containing multiple mitochondria while others are completely void. This heterogeneous partitioning is conserved …

Mitochondrial Efficiency: Bridging Early-Life Environment And Organismal Performance, Kayla E. Lichtner

Master’s Theses

Mitochondria operate at the forefront of organismal-environmental interactions. Despite remarkable diversity in mitochondrial function both within and among species, all mitochondria serve a universal role in facilitating the flow of energy between organisms and their environment. Energetic efficiency, the way in which organisms assimilate and transform environmental substrate into physiological currency, is a major determinant of organismal performance. Although previous studies have shown that early-life environment can have lasting effects on metabolism, the underlying mechanisms driving the emergence of mitochondrial phenotypic variation remain poorly understood. Leach’s storm-petrels (Hydrobates leucorhous) provide a valuable opportunity to investigate longitudinal hypotheses of …

Opa1-Mediated Mitochondrial Dynamics In Myogenic Differentiation Of C2c12 Myoblasts, Daniel Eloy Bazan

Theses and Dissertations

Mitochondria play a pivotal role in metabolic energy production, cellular signaling, and apoptosis. To carry out these key cellular roles, mitochondria dynamically balance their organization through opposing including fusion and fission processes. The balance between mitochondrial fusion and fission is regulated by key proteins such as OPA1 (optic atrophy 1) and OMA1 (overlapping activity with metalloprotease). More recently, mitochondria have been increasingly revealed to play key roles in cellular differentiation, where metabolic demands are reprogrammed. This study aims to elucidate the specific roles of OPA1 and OMA1 in the differentiation of C2C12 myoblast cells into myotubes.

Our data demonstrates that …

Improved Autofluorescence Lifetime Decay Analysis For Identification Of Cellular Autofluorescence Biomarkers For Label-Free, Single-Cell Assessment Of Mitochondrial Membrane Potential, Olivia Isabel Kolenc

Graduate Theses and Dissertations

Optical imaging of metabolism using the autofluorescence of the metabolic cofactors NADH, NADPH, and FAD has a wide range of sensitivities and the capability to collect a great deal of metabolic information. Multiphoton microscopy (MPM) is a non-invasive, label-free optical imaging technique capable of performing fluorescence lifetime imaging (FLIM) using time correlated single photon counting (TCSPC). However, autofluorescence FLIM presents a challenge in collecting sufficient photons to provide adequate signal to noise ratios (SNR) for analysis. Additionally, the specificity of autofluorescence biomarkers of metabolism has not been well-defined. Contextualizing these autofluorescence measures using established functional biomarkers can improve interpretability of …

Investigating The Threshold Of Opa1-Mediated Mitochondrial Fusion In Shsy5y Cells, Jorge Alberto Elizondo

Theses and Dissertations

Mitochondrial dynamics occurring under stress-induced conditions in SHSY5Y neuroblastoma cells provide insight into the OPA1-mediated mitochondrial fusion threshold in cells of varying energetic demands. Mitochondria are dynamic structures that are continuously balancing fusion and fission, depending on cellular needs. The ability to fuse and divide relies on the maintenance of the mitochondrial transmembrane potential. Stress-induced conditions in SHSY5Y cells were induced via utilization of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore that disrupts the transmembrane potential. OMA1 protein reacts to the loss of transmembrane potential and subsequently cleaves the fusion-active isoforms of OPA1, L-OPA1. This causes an accumulation of S-OPA1, the …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

A Natural Short Sleep Mutation Promotes Longevity Through Mitochondrial Respiration In Drosophila, Pritika Pandey

LSU Doctoral Dissertations

Aging is an irreversible process characterized by progressive physiological decline and an increased risk of metabolic disorders, cognitive impairment, cardiovascular diseases, and neurodegeneration. Disruptions to the circadian clock—whether due to genetic mutations or behavioral factors—accelerate aging and age-related pathologies, highlighting a strong link between circadian regulation and longevity. However, certain individuals harbor a dec2^P384R mutation, which enables natural short sleep without the detrimental effects of chronic sleep deprivation. This suggests that these individuals have evolved adaptations that activate pro-health pathways, allowing them to function optimally with reduced sleep. To investigate the genetic mechanisms underlying these changes, we developed a …

Hydrolysis Of The Acetyl-Coa Allosteric Activator By Staphylococcus Aureus Pyruvate Carboxylase, Amanda J. Laseke, Jeremy R. Lohman, Martin St. Maurice

Biological Sciences Faculty Research and Publications

Pyruvate carboxylase (PC) catalyzes the carboxylation of pyruvate to oxaloacetate which serves as an important anaplerotic reaction to replenish citric acid cycle intermediates. In most organisms, the PC-catalyzed reaction is allosterically activated by acetyl-coenzyme A. It has previously been reported that vertebrate PC can catalyze the hydrolysis of acetyl-CoA, offering a potential means for the enzyme to attenuate its allosteric activation. However, in the years since this initial report, there has been no further investigation of this phenomenon. The allosteric binding site for acetyl-CoA is now well characterized, enabling more detailed studies on acetyl-CoA hydrolysis at the allosteric site. Here, …

Mitochondrial A3 Adenosine Receptor As A Mechanism For The Protective Effects Of A3ar Agonists On Chemotherapy-Induced Neuropathic Pain, Timothy M. Doyle, Kali Janes, Wen Hua Xiao, Grant R. Kolar, Hans F. Luecke, Michael Anne Gratton, Dilip K. Tosh, Kenneth A. Jacobson, Gary J. Bennett, Daniela Salvemini

Biological Sciences Faculty Research & Creative Works

Alterations in mitochondrial function are the linchpin in numerous disease states including in the development of chemotherapy-induced neuropathic pain (CIPN), a major dose-limiting toxicity of widely used chemotherapeutic cytotoxins. In CIPN, mitochondrial dysfunction is characterized by deficits in mitochondrial bioenergetics (e.g., decreased ATP production) that are thought to drive the degeneration of the peripheral nerve sensory axon terminal sensory arbors in the skin (the intraepidermal nerve fibers; IENFs) and induce abnormal spontaneous discharge in peripheral nerve sensory axons. Preserving mitochondrial function is anticipated to prevent CIPN. We have now discovered that the G-protein-coupled receptor, A3 adenosine receptor subtype (A3AR), is …

Assessing The Role Of Daily Thermal Fluctuations In The Performance Of Mitochondrial Energy Transduction Of The Centrarchid, Lepomis Cyanellus, Grayson Hofmann

Masters Theses

Freshwater systems are affected by current climate extremes, forcing species found in these systems to withstand drastic changes in temperature. Temperature changes affect these organisms by altering their metabolic rate and energy balance. Increases in temperature can lead to an increase in oxygen consumption, which ultimately increases the need for more energy production. Mitochondrial energy transduction of green sunfish (Lepomis cyanellus) and many other fish species after a thermal insult, has hardly been explored. This study complements the limited research available on mitochondrial function in similar species, as they ignore the possibility of consecutive thermal events, which are …

Investigating The Physiological, Metabolomic, And Transcriptomic Changes In Response To Telomerase Deletion In Saccharomyces Cerevisiae, Taizina Momtareen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Telomerase is an enzyme found in rapidly dividing cells that maintains chromosome ends and prevents the loss of genetic information during cell division. When telomerase is inactive, cells gradually lose their telomeres and eventually stop dividing. In yeast, a rare subset of cells can bypass this growth arrest by switching to a recombination-based mechanism to maintain telomeres. Therefore, yeast provides a powerful system to study this adaptation, as telomerase-deficient strains can generate 'survivors' that mimic the Alternative Lengthening of Telomeres (ALT) pathway observed in some human tumors. In this work, my goal was to examine how a telomerase-null (TLC1 …

Mitochondrial Network Reorganization And Transient Expansion During Oligodendrocyte Generation, Xhoela Bame, Robert A. Hill

Dartmouth Scholarship

Oligodendrocyte precursor cells (OPCs) give rise to myelinating oligodendrocytes of the brain. This process persists throughout life and is essential for recovery from neurodegeneration. To better understand the cellular checkpoints that occur during oligodendrogenesis, we determined the mitochondrial distribution and morphometrics across the oligodendrocyte lineage in mouse and human cerebral cortex. During oligodendrocyte generation, mitochondrial content expands concurrently with a change in subcellular partitioning towards the distal processes. These changes are followed by an abrupt loss of mitochondria in the oligodendrocyte processes and myelin, coinciding with sheath compaction. This reorganization and extensive expansion and depletion take 3 days. Oligodendrocyte mitochondria …

Support For Climate Shaping The Mitochondrial Dna Contact Zone In The Audubon's Warbler, Kyana Nina Montoya

Biology ETDs

Mitochondrial introgression has potential consequences for physiology and adaptation, but its causes are poorly understood. The Audubon’s Warbler (AUWA; Setophaga coronata auduboni) provides a case study to examine those causes as mitochondrial introgression has swept through part of the range. The northern mitochondrial genome (mtDNA) introgressed from the Myrtle Warbler (MYWA; S. c. coronata) and is 4% divergent from the southern mtDNA. Incomplete introgression suggests discordant AUWAs conferred a selective advantage in the north; it was hypothesized that energetic demands associated with migration formed this advantage. We tested two hypotheses to explain partial introgression and the mtDNA distribution …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Ablation Of Sam50 Is Associated With Fragmentation And Alterations In Metabolism In Murine And Human Myotubes, Bryanna Shao, Mason Killion, Ashton Oliver, Chia Vang, Faben Zeleke, Kit Neikirk, Zer Vue, Edgar Garza‐Lopez, Jian‐Qiang Shao, Margaret Mungai, Jacob Lam, Qiana Williams, Christopher T. Altamura, Aaron Whiteside, Kinuthia Kabugi, Jessica Mckenzie, Maria Ezedimma, Han Le, Alice Koh, Estevão Scudese, Larry Vang, Andrea G. Marshall, Amber Crabtree, Janelle I. Tanghal, Dominique Stephens, Ho‐Jin Koh, Brenita C. Jenkins, Sandra A. Murray, Anthonya T. Cooper, Clintoria Williams, Steven M. Damo10 M. Damo, Melanie R. Mcreynolds, Jennifer A. Gaddy Gaddy, Celestine N. Wanjalla, Heather K. Beasley, Antentor Hinton Jr.

Biology Faculty Research

The sorting and assembly machinery (SAM) Complex is responsible for assembling β‐barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space

bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block‐face‐scanning electron microscopy and computer‐assisted …

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

9s1r Nullomer Peptide Induces Mitochondrial Pathology, Metabolic Suppression, And Enhanced Immune Cell Infiltration, In Triple-Negative Breast Cancer Mouse Model, Nilufar Ali, Cody Wolf, Swarna Kanchan, Shivakumar R. Veerabhadraiah, Laura Bond, Matthew W. Turner, Cheryl L. Jorcyk, Greg Hampikian

Biology Faculty Publications and Presentations

Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group of species. Primes are those nullomers that have not been detected in the genome of any species. 9S1R is a 5-aa peptide prime sequence attached to 5-arginine aa, used to treat triple negative breast cancer (TNBC) in an in vivo mouse model. This unique peptide, administered with a trehalose carrier (9S1R-NulloPT), offers enhanced solubility and exhibits distinct anti-cancer effects against TNBC. In our study, we investigated the effect of 9S1R-NulloPT on tumor growth, metabolism, metastatic burden, tumor immune-microenvironment (TME), and transcriptome of aggressive mouse …

Identification Of Mimas, A Multifunctional Mega-Assembly Integrating Metabolic And Respiratory Biogenesis Factors Of Mitochondria, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

The mitochondrial inner membrane plays central roles in bioenergetics and metabolism and contains several established membrane protein complexes. Here, we report the identification of a mega-complex of the inner membrane, termed mitochondrial multifunctional assembly (MIMAS). Its large size of 3 MDa explains why MIMAS has escaped detection in the analysis of mitochondria so far. MIMAS combines proteins of diverse functions from respiratory chain assembly to metabolite transport, dehydrogenases, and lipid biosynthesis but not the large established supercomplexes of the respiratory chain, ATP synthase, or prohibitin scaffold. MIMAS integrity depends on the non-bilayer phospholipid phosphatidylethanolamine, in contrast to respiratory supercomplexes whose …

Importance Of Conserved Hydrophobic Pocket Region In Yeast Mitoribosomal Ml44 Protein For Mitotranslation And Transcript Preference, Jodie M. Box, Margo E. Higgins, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

The mitochondrial ribosome (mitoribosome) is responsible for the synthesis of key oxidative phosphorylation subunits encoded by the mitochondrial genome. Defects in mitoribosomal function therefore can have serious consequences for the bioenergetic capacity of the cell. Mutation of the conserved mitoribosomal mL44 protein has been directly linked to childhood cardiomyopathy and progressive neurophysiology issues. To further explore the functional significance of the mL44 protein in supporting mitochondrial protein synthesis, we have performed a mutagenesis study of the yeast mL44 homolog, the MrpL3/mL44 protein. We specifically investigated the conserved hydrophobic pocket region of the MrpL3/mL44 protein, where the known disease-related residue …

Repatriation And A Biological Profile Of Indigenous Remains Of West Texas, Haley P. Rebardi

Graduate Student Theses, Dissertations, & Professional Papers

The Native American Graves Protection and Repatriation Act (NAGPRA) was created in response to the injustice, mishandling, looting, and trafficking of Native American remains and cultural artifacts. However, even with the latest amendment in December of 2023, there are still gray areas in the context and language. Notably, an issue with NAGPRA is the act only includes institutions and organizations that receive and are supported by Federal funding. Consequently, the act does not cover private collections. The main concern in these contexts is the lack of communication, awareness, and/or permission with and from descendant tribes or potential descendants when it …

Trehalose Enhances Mitochondria Deficits In Human Npc1 Mutant Fibroblasts But Disrupts Mouse Purkinje Cell Dendritic Growth Ex Vivo., Collin M Macleod, Fawad A K Yousufzai, Liam T Spencer, Sarah Kim, Lucianne A Rivera-Rosario, Zerian D Barrera, Lindsay Walsh, Claude Krummenacher, Benjamin Carone, Ileana Soto

College of Science & Mathematics Departmental Research

Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblasts in vitro and in mouse developmental Purkinje cells ex vivo. We …

Mitochondrial Transplantation And Transfer: The Promising Method For Diseases, Gökhan Burçi̇n Kubat

Turkish Journal of Biology

Mitochondria are organelles that serve as the powerhouses for cellular bioenergetics in eukaryotic cells. It is responsible for mitochondrial adenosine triphosphate (ATP) generation, cell signaling and activity, calcium balance, cell survival, proliferation, apoptosis, and autophagy. Mitochondrial transplantation is a promising disease therapy that involves the recovery of mitochondrial dysfunction using isolated functioning mitochondria. The objective of the present article is to provide current knowledge on natural mitochondrial transfer processes, in vitro and in vivo applications of mitochondrial transplantation, clinical trials, and challenges associated with mitochondrial transplantation.

The N-Terminal Region Of Yeast Mitoribosomal Mrp7/Bl27m Protein Serves To Optimize Translation Of Nascent Chains Competent For Oxphos Complex Assembly, Jessica M. Anderson, Jodie M. Box, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

The extreme N-terminal residues of the mitochondrial ribosomal bL27m proteins reside within the ribosomal peptidyl transferase center (PTC) and are conserved from their bacterial ancestors. Mutation or truncation of the N-terminal region of the yeast Mrp7/bL27m protein did not inhibit protein synthesis but significantly impacted the efficacy of the mitochondrial translational process with respect to yielding proteins competent to assemble into functional oxidative phosphorylation enzymes. The requirement for the N-terminal residues of Mrp7/bL27m to support normal mitotranslation was more apparent under respiratory growth. We demonstrate that the N-terminal region of Mrp7/bL27m impacts the environment of the PTC and speculate the …

Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?, Claire Pearson

Honors Theses

Apoptosis is a type of regulated cell death important for normal embryonic development and maintenance of adult tissues by removing excess or dysfunctional cells to ensure proper functioning of organs. The Bcl-2 family of proteins determines whether apoptosis remains suppressed or becomes activated through the balance of interactions among pro-survival and pro-death members. A defining feature of the Bcl-2 family is a BH3 domain that drives interactions between the family members. Isoform 1 of the voltage dependent anion channel (VDAC1) has an important role in metabolism, but was recently found to have high homology with known BH3 domains. This study …

Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany

Honors Theses

Mitochondrial outer membrane permeabilization (MOMP) by Bax oligomerization triggers apoptosis. BCl-2 family proteins, classified as BH3 only proteins, pro-survival proteins, or pro-apoptotic proteins, control apoptosis partly through their agonist or antagonistic effects on Bax, which are mediated by their conserved BH3 domains. All BH3 domains form an alpha helix containing 5-7 conserved hydrophobic residues, designated H0-H5, and one conserved aspartic acid that drive interaction with Bax and other ‘multi-domain’ BCl-2 members. BH3 agonists induce Bax oligomerization, while BH3 antagonists sequester Bax to prevent MOMP. We discovered that voltage dependent anion channels (VDACs) in the MOM contain a putative BH3-like domain …

Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter

Biomedical Engineering Theses & Dissertations

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the …

Myo19 Tethers Mitochondria To Endoplasmic Reticulum-Associated Actin To Promote Mitochondrial Fission, Stephen M. Coscia, Cameron P. Thompson, Qing Tang, Elana E. Baltrusaitis, Joseph A. Rhodenhiser, Omar A. Quintero, E. Michael Ostap, Melike Lakadamyali, Erika L. Holzbaur

Biology Faculty Publications

Mitochondrial homeostasis requires a dynamic balance of fission and fusion. The actin cytoskeleton promotes fission, and we found that the mitochondrially localized myosin, myosin 19 (Myo19), is integral to this process. Myo19 knockdown induced mitochondrial elongation, whereas Myo19 overexpression induced fragmentation. This mitochondrial fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding but not by mutations predicted to affect the working stroke of the motor that preserve ATPase activity. Super-resolution imaging indicated a dispersed localization of Myo19 on mitochondria, which we found to be dependent on metaxins. These observations suggest that Myo19 acts …

Characterization Of The Roles Of Mitochondria In The Toxicity Of Α-Synuclein In A Respiratory Cell Model, Breonna Elizabeth Gillespie

Browse all Theses and Dissertations

Although α-synuclein (α-syn) has been linked genetically and pathologically to Parkinson’s disease, the mechanism by which it drives disease pathogenesis is not fully understood. When α-syn is overexpressed in yeast, it forms abnormal cytoplasmic accumulations and leads to cell death, resembling the phenotypes observed in neurons. Such yeast models have been widely used to uncover molecular mechanisms of α-syn toxicity, but the induction of α-syn relies on growing yeast in galactose, a fermentable carbon source. Yeast does not require cellular respiration when grown in galactose, thus limiting the understanding of α-syn toxicity when cellular respiration is essential for neurons. We …

Excess Dietary Sugar Alters Colonocyte Metabolism And Impairs The Proliferative Response To Damage, Ansen H.P. Burr, Junyi Ji, Kadir Ozler, Heather L. Mentrup, Onur Eskiocak, Brian Yueh, Rachel Cumberland, Ashley V. Menk, Natalie Rittenhouse, Christopher Marshall, Pailin Chiaranunt, Xiaoyi Zhang, Lauren Mullinax, Abigail Overacre-Delgoffe, Vaughn S. Cooper, Amanda C. Poholek, Greg M. Delgoffe, Kevin P. Mollen, Semir Beyaz, Timothy W. Hand

Biological Sciences Faculty Research and Publications

Background & Aims

The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown.

Methods

Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells. …