scholarly journals An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses

2018 ◽  
Vol 19 (10) ◽  
pp. 3100 ◽  
Author(s):  
Szymon Kaczanowski ◽  
Joanna Klim ◽  
Urszula Zielenkiewicz
Keyword(s):  
Neurodegenerative Diseases ◽  
Anaerobic Respiration ◽  
Nobel Prize Winner ◽  
Mitochondrial Activity ◽  
Otto Warburg ◽  
Pathological Aging ◽  
Phylogenetic Studies ◽  
Oxidative Respiration ◽  
Apoptotic Factors ◽  
The Warburg Effect

Otto Warburg, a Nobel prize winner, observed that cancer cells typically “switch” from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage induces neoplastic transformation. In contrast, pathological aging is observed mainly in neuron cells in neurodegenerative diseases. Oxidative respiration is particularly active in neurons. There is inverse comorbidity between cancer and neurodegenerative diseases. This led to the creation of the “inverse Warburg hypothesis”, according to which excessive mitochondrial activity induces pathological aging. The findings of our studies suggest that both the Warburg effect and the “inverse Warburg hypothesis” can be elucidated by the activation or suppression of apoptosis through oxidative respiration. The key outcome of our phylogenetic studies was the discovery that apoptosis and apoptosis-like cell death evolved due to an evolutionary “arms race” conducted between “prey” protomitochondrion and “predator” primitive eukaryotes. The ancestral protomitochondrial machinery produces and releases toxic mitochondrial proteins. Extant apoptotic factors evolved from these toxins. Our experiments indicate that the mitochondrial machinery is directly involved in adaptation to aerobic conditions. Additionally, our hypothesis is supported by the fact that different apoptotic factors are directly involved in respiration.

scholarly journals Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3310 ◽  
Author(s):  
Namsi ◽  
Nury ◽  
Khan ◽  
Leprince ◽  
Vaudry ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Viability ◽  
Neuronal Differentiation ◽  
Nerve Cell ◽  
Cell Damage ◽  
Mitochondrial Activity ◽  
Cell Functions ◽  
N2a Cells ◽  
Topographical Distribution ◽  
The Impact

Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10−14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.

scholarly journals L-Glucose: Another Path to Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 850 ◽  
Author(s):  
Koki Ono ◽  
Shota Takigawa ◽  
Katsuya Yamada
Keyword(s):  
Cancer Cells ◽  
Cancer Diagnosis ◽  
Warburg Effect ◽  
Mirror Image ◽  
Mitochondrial Activity ◽  
Cell Aggregates ◽  
Naturally Occurring ◽  
Metabolic Heterogeneity ◽  
The Warburg Effect

Cancerous tumors comprise cells showing metabolic heterogeneity. Among numerous efforts to understand this property, little attention has been paid to the possibility that cancer cells take up and utilize otherwise unusable substrates as fuel. Here we discuss this issue by focusing on l-glucose, the mirror image isomer of naturally occurring d-glucose; l-glucose is an unmetabolizable sugar except in some bacteria. By combining relatively small fluorophores with l-glucose, we generated fluorescence-emitting l-glucose tracers (fLGs). To our surprise, 2-NBDLG, one of these fLGs, which we thought to be merely a control substrate for the fluorescent d-glucose tracer 2-NBDG, was specifically taken up into tumor cell aggregates (spheroids) that exhibited nuclear heterogeneity, a major cytological feature of malignancy in cancer diagnosis. Changes in mitochondrial activity were also associated with the spheroids taking up fLG. To better understand these phenomena, we review here the Warburg effect as well as key studies regarding glucose uptake. We also discuss tumor heterogeneity involving aberrant uptake of glucose and mitochondrial changes based on the data obtained by fLG. We then consider the use of fLGs as novel markers for visualization and characterization of malignant tumor cells.

scholarly journals Caloric Restriction and the Nutrient-Sensing PGC-1αin Mitochondrial Homeostasis: New Perspectives in Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daniele Lettieri Barbato ◽  
Sara Baldelli ◽  
Beatrice Pagliei ◽  
Katia Aquilano ◽  
Maria Rosa Ciriolo
Keyword(s):  
Neurodegenerative Diseases ◽  
Caloric Restriction ◽  
Mitochondrial Biogenesis ◽  
Dietary Intervention ◽  
Current Knowledge ◽  
Nutritional Intervention ◽  
Nutrient Sensing ◽  
Mitochondrial Activity ◽  
Beneficial Effects ◽  
And Function

Mitochondrial activity progressively declines during ageing and in many neurodegenerative diseases. Caloric restriction (CR) has been suggested as a dietary intervention that is able to postpone the detrimental aspects of aging as it ameliorates mitochondrial performance. This effect is partially due to increased mitochondrial biogenesis. The nutrient-sensing PGC-1αis a transcriptional coactivator that promotes the expression of mitochondrial genes and is induced by CR. It is believed that many of the mitochondrial and metabolic benefits of CR are due to increased PGC-1αactivity. The increase of PGC-1αis also positively linked to neuroprotection and its decrement has been involved in the pathogenesis of many neurodegenerative diseases. This paper aims to summarize the current knowledge about the role of PGC-1αin neuronal homeostasis and the beneficial effects of CR on mitochondrial biogenesis and function. We also discuss how PGC-1α-governed pathways could be used as target for nutritional intervention to prevent neurodegeneration.

scholarly journals Author Correction: Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gyula Bencze ◽  
Szilvia Bencze ◽  
Keith D. Rivera ◽  
James D. Watson ◽  
Mate Hidvegi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Warburg Effect ◽  
Mitochondrial Activity ◽  
The Warburg Effect

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Oxidative respiration through the bd-I and cbb3 oxidases is required for Vibrio cholerae pathogenicity and proliferation in vivo.

2021 ◽  
Author(s):  
Andrew John Van Alst ◽  
Lucas Maurice Demey ◽  
Victor DiRita
Keyword(s):  
Vibrio Cholerae ◽  
Anaerobic Respiration ◽  
Bacterial Pathogen ◽  
Population Expansion ◽  
Amplicon Sequencing ◽  
Electron Acceptors ◽  
Infant Mouse ◽  
Small Intestinal ◽  
Oxidative Respiration

Vibrio cholerae respires both aerobically and anaerobically and, while oxygen may be available to it during infection, other terminal electron acceptors are proposed for population expansion during infection. Unlike gastrointestinal pathogens that stimulate significant inflammation leading to elevated levels of oxygen or alternative terminal electron acceptors, V. cholerae infections are not understood to induce a notable inflammatory response. To ascertain the respiration requirements of V. cholerae during infection, we used Multiplex Genome Editing by Natural Transformation (MuGENT) to create V. cholerae strains lacking aerobic or anaerobic respiration. V. cholerae strains lacking aerobic respiration were attenuated in infant mice 10 5 -fold relative to wild type, while strains lacking anaerobic respiration had no colonization defect, contrary to earlier work suggesting a role for anaerobic respiration during infection. Using several approaches, including one we developed for this work termed Comparative Multiplex PCR Amplicon Sequencing (CoMPAS), we determined that the bd-I and cbb3 oxidases are essential for small intestinal colonization of V. cholerae in the infant mouse. The bd-I oxidase was also determined as the primary oxidase during growth outside the host, making V. cholerae the only example of a Gram-negative bacterial pathogen in which a bd-type oxidase is the primary oxidase for energy acquisition inside and outside of a host.

scholarly journals A minimal model for explaining the higher ATP production in the Warburg effect

2015 ◽  
Author(s):  
Stefan Schuster ◽  
Daniel Boley ◽  
Philip Möller ◽  
Christoph Kaleta
Keyword(s):  
Minimal Model ◽  
Warburg Effect ◽  
Flux Distribution ◽  
Striated Muscle ◽  
Cell Types ◽  
High Yield ◽  
Activated Lymphocytes ◽  
Atp Production ◽  
Otto Warburg ◽  
The Warburg Effect

For producing ATP, tumor cells rely on glycolysis leading to lactate to about the same extent as on respiration. Thus, they use a higher fraction of glycolysis than the corresponding healthy cells. This is known as the Warburg effect (named after German biochemist Otto Warburg) and also applies to striated muscle cells, activated lymphocytes and microglia, endothelial cells and several other cell types. This effect is paradoxical at first sight because the ATP yield of glycolysis is much lower than that of respiration. Although a straightforward explanation is that glycolysis allows a higher ATP production rate, the question arises why the cell does not re-allocate protein to the high-yield pathway of respiration. We tackle this question by a minimal model only including three combined reactions. We consider the case where the cell can allocate protein on several enzymes in a varying distribution and model this by a linear programming problem in which not only the rates but also the maximal velocities are variable. Depending on side conditions and on protein costs, this leads to pure respiration, pure glycolysis, and respirofermentation as a mixed flux distribution.

scholarly journals Glucose Metabolism in Cancer: The Warburg Effect and Beyond

2021 ◽  
pp. 3-15 ◽  
Author(s):  
Sminu Bose ◽  
Cissy Zhang ◽  
Anne Le
Keyword(s):  
Glucose Metabolism ◽  
Molecular Biology ◽  
Warburg Effect ◽  
Scientific Community ◽  
Cancer Metabolism ◽  
Cancer Therapies ◽  
Otto Warburg ◽  
New Cancer Therapies ◽  
Open The Doors ◽  
The Warburg Effect

AbstractOtto Warburg observed a peculiar phenomenon in 1924, unknowingly laying the foundation for the field of cancer metabolism. While his contemporaries hypothesized that tumor cells derived the energy required for uncontrolled replication from proteolysis and lipolysis, Warburg instead found them to rapidly consume glucose, converting it to lactate even in the presence of oxygen. The significance of this finding, later termed the Warburg effect, went unnoticed by the broader scientific community at that time. The field of cancer metabolism lay dormant for almost a century awaiting advances in molecular biology and genetics, which would later open the doors to new cancer therapies [2, 3].

scholarly journals The Role of Mitochondrial Calcium Homeostasis in Alzheimer’s and Related Diseases

2020 ◽  
Vol 21 (23) ◽  
pp. 9153
Author(s):  
Kerry C. Ryan ◽  
Zahra Ashkavand ◽  
Kenneth R. Norman
Keyword(s):  
Neurodegenerative Diseases ◽  
Calcium Signaling ◽  
Mitochondrial Function ◽  
Reciprocal Relationship ◽  
Mitochondrial Activity ◽  
Mitochondrial Calcium ◽  
Protein Homeostasis ◽  
Neuronal Function ◽  
The Impact

Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer’s disease (AD). A close reciprocal relationship exists between calcium signaling and mitochondrial function. Growing evidence in a variety of AD models indicates that calcium dyshomeostasis drastically alters mitochondrial activity which, in turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which calcium impairs mitochondrial function in AD, focusing on the impact of calcium in endoplasmic reticulum (ER)–mitochondrial communication, mitochondrial transport, oxidative stress, and protein homeostasis. This review also summarizes recent data that highlight the need for exploring the mechanisms underlying calcium-mediated mitochondrial dysfunction while suggesting potential targets for modulating mitochondrial calcium levels to treat neurodegenerative diseases such as AD.

scholarly journals The Role of Glucose Metabolism and Glucose-Associated Signalling in Cancer

2007 ◽  
Vol 1 ◽  
pp. 1177391X0700100 ◽  
Author(s):  
Rainer Wittig ◽  
Johannes F. Coy
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Genetic Manipulation ◽  
Aerobic Glycolysis ◽  
Nobel Laureate ◽  
Pentose Phosphate ◽  
Pharmacological Intervention ◽  
Otto Warburg ◽  
The Warburg Effect ◽  
Glycolytic Phenotype

Aggressive carcinomas ferment glucose to lactate even in the presence of oxygen. This particular metabolism, termed aerobic glycolysis, the glycolytic phenotype, or the Warburg effect, was discovered by Nobel laureate Otto Warburg in the 1920s. Since these times, controversial discussions about the relevance of the fermentation of glucose by tumours took place; however, a majority of cancer researchers considered the Warburg effect as a non-causative epiphenomenon. Recent research demonstrated, that several common oncogenic events favour the expression of the glycolytic phenotype. Moreover, a suppression of the phenotypic features by either substrate limitation, pharmacological intervention, or genetic manipulation was found to mediate potent tumour-suppressive effects. The discovery of the transketolase-like 1 (TKTL1) enzyme in aggressive cancers may deliver a missing link in the interpretation of the Warburg effect. TKTL1-activity could be the basis for a rapid fermentation of glucose in aggressive carcinoma cells via the pentose phosphate pathway, which leads to matrix acidification, invasive growth, and ultimately metastasis. TKTL1 expression in certain non-cancerous tissues correlates with aerobic formation of lactate and rapid fermentation of glucose, which may be required for the prevention of advanced glycation end products and the suppression of reactive oxygen species. There is evidence, that the activity of this enzyme and the Warburg effect can be both protective or destructive for the organism. These results place glucose metabolism to the centre of pathogenesis of several civilisation related diseases and raise concerns about the high glycaemic index of various food components commonly consumed in western diets.

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