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International Journal of Molecular... Dec 2020In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in...
In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in respiratory substrates produced during photosynthetic CO assimilation and function in keeping the metabolic and redox homeostasis in the light in eukaryotic cells, based on the interactions among the cytosol, chloroplasts, and mitochondria. Here, we first characterize LER in photosynthetic prokaryote cyanobacteria, in which respiration and photosynthesis share their metabolisms and electron transport chains in one cell. From the physiological analysis, the cyanobacterium sp. PCC 6803 performs LER, similar to eukaryotic algae, which shows a capacity comparable to the net photosynthetic O evolution rate. Although the respiratory and photosynthetic electron transports share the interchain, LER was uncoupled from photosynthetic electron transport. Mutant analyses demonstrated that LER is motivated by the substrates directly provided by photosynthetic CO assimilation, but not by glycogen. Further, the light-dependent activation of LER was observed even with exogenously added glucose, implying a regulatory mechanism for LER in addition to the substrate amounts. Finally, we discuss the physiological significance of the large capacity of LER in cyanobacteria and eukaryotic algae compared to those in plants that normally show less LER.
Topics: Cell Respiration; Cyanobacteria; Electron Transport; Light; Oxidation-Reduction; Oxygen; Photosynthesis
PubMed: 33396191
DOI: 10.3390/ijms22010342 -
Biochimica Et Biophysica Acta Apr 2012The reactions between Complex IV (cytochrome c oxidase, CcOX) and nitric oxide (NO) were described in the early 60's. The perception, however, that NO could be... (Review)
Review
BACKGROUND
The reactions between Complex IV (cytochrome c oxidase, CcOX) and nitric oxide (NO) were described in the early 60's. The perception, however, that NO could be responsible for physiological or pathological effects, including those on mitochondria, lags behind the 80's, when the identity of the endothelial derived relaxing factor (EDRF) and NO synthesis by the NO synthases were discovered. NO controls mitochondrial respiration, and cytotoxic as well as cytoprotective effects have been described. The depression of OXPHOS ATP synthesis has been observed, attributed to the inhibition of mitochondrial Complex I and IV particularly, found responsible of major effects.
SCOPE OF REVIEW
The review is focused on CcOX and NO with some hints about pathophysiological implications. The reactions of interest are reviewed, with special attention to the molecular mechanisms underlying the effects of NO observed on cytochrome c oxidase, particularly during turnover with oxygen and reductants.
MAJOR CONCLUSIONS AND GENERAL SIGNIFICANCE
The NO inhibition of CcOX is rapid and reversible and may occur in competition with oxygen. Inhibition takes place following two pathways leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) of the enzyme reduced, or a more labile nitrite-derivative (CcOX-NO(2)(-)) of the enzyme oxidized, and during turnover. The pathway that prevails depends on the turnover conditions and concentration of NO and physiological substrates, cytochrome c and O(2). All evidence suggests that these parameters are crucial in determining the CcOX vs NO reaction pathway prevailing in vivo, with interesting physiological and pathological consequences for cells.
Topics: Animals; Cell Respiration; Cytochromes c; Electron Transport Complex IV; Humans; Models, Biological; Nitric Oxide; Oxidation-Reduction; Oxygen; Signal Transduction
PubMed: 21939634
DOI: 10.1016/j.bbabio.2011.09.002 -
The New Phytologist May 2011The oxygen availability to plant tissues can vary strongly in time and space. To endure short- or long-term oxygen deprivation, plants evolved a series of metabolic and... (Review)
Review
The oxygen availability to plant tissues can vary strongly in time and space. To endure short- or long-term oxygen deprivation, plants evolved a series of metabolic and morphological adaptations that have been extensively studied. However, our knowledge of the molecular regulation of these processes is not as well understood. In this review, the recent findings on the molecular effectors that regulate the response of higher plants to oxygen deficiency are discussed. Although no direct oxygen sensor has been discovered in plants so far, mechanisms that perceive low-oxygen derived signals have been reported, involving different sets of transcription factors (TFs). The ERF (Ethylene Responsive Factor) family especially appears to play a crucial role in the determination of survival to reduced oxygen availability in Arabidopsis and rice. This class of TFs displays a broad range of targets, being involved in both the metabolic reprogramming and the morphological adaptations exploited by plants when subjected to low-oxygen conditions.
Topics: Adaptation, Physiological; Cell Hypoxia; Models, Biological; Oxygen; Plants; Signal Transduction
PubMed: 21091695
DOI: 10.1111/j.1469-8137.2010.03562.x -
Biophysical Journal Feb 2003Respiratory deficient cell lines are being increasingly used to elucidate the role of mitochondria and to understand the pathophysiology of mitochondrial genetic... (Comparative Study)
Comparative Study
Respiratory deficient cell lines are being increasingly used to elucidate the role of mitochondria and to understand the pathophysiology of mitochondrial genetic disease. We have investigated the oxygen consumption rates and oxygen concentration in wild-type (WT) and mitochondrial DNA (mtDNA) depleted (rho(0)) Molt-4 cells. Wild-type Molt-4 cells have moderate oxygen consumption rates, which were significantly reduced in the rho(0) cells. PCMB (p-chloromercurobenzoate) inhibited the oxygen consumption rates in both WT and rho(0) cells, whereas potassium cyanide decreased the oxygen consumption rates only in WT Molt-4 cells. Menadione sodium bisulfite (MSB) increased the oxygen consumption rates in both cell lines, whereas CCCP (carbonyl cyanide m-chlorophenylhydrazone) stimulated the oxygen consumption rates only in WT Molt-4 cells. Superoxide radical adducts were observed in both WT and rho(0) cells when stimulated with MSB. The formation of this adduct was inhibited by PCMB but not by potassium cyanide. These results suggest that the reactive oxygen species (ROS) induced by MSB were at least in part produced via a mitochondrial independent pathway. An oxygen gradient between the extra- and intracellular compartments was observed in WT Molt-4 cells, which further increased when cells were stimulated by CCCP and MSB. The results are consistent with our earlier findings suggesting that such oxygen gradients may be a general phenomenon found in most or all cell systems under appropriate conditions.
Topics: Benzoates; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cell Respiration; Electron Spin Resonance Spectroscopy; Extracellular Space; Humans; Intracellular Fluid; Leukemia; Mitochondria; Mutagenesis, Site-Directed; Mutation; Oximetry; Oxygen; Oxygen Consumption; Potassium Cyanide; Reactive Oxygen Species; Spin Trapping; Succinimides; Tumor Cells, Cultured; p-Chloromercuribenzoic Acid
PubMed: 12547809
DOI: 10.1016/S0006-3495(03)74944-3 -
International Journal of Molecular... Oct 2018Otto Warburg, a Nobel prize winner, observed that cancer cells typically "switch" from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage... (Review)
Review
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.
Topics: Aging; Animals; Apoptosis; Cell Respiration; Cell Transformation, Neoplastic; Energy Metabolism; Eukaryota; Humans; Mitochondria; Neoplasms; Neurodegenerative Diseases; Oxygen; Symbiosis
PubMed: 30308966
DOI: 10.3390/ijms19103100 -
Cellular and Molecular Life Sciences :... Jun 2012In recent years, significant progress has been achieved in the sensing and imaging of molecular oxygen (O(2)) in biological samples containing live cells and tissue. We... (Review)
Review
In recent years, significant progress has been achieved in the sensing and imaging of molecular oxygen (O(2)) in biological samples containing live cells and tissue. We review recent developments in the measurement of O(2) in such samples by optical means, particularly using the phosphorescence quenching technique. The main types of soluble O(2) sensors are assessed, including small molecule, supramolecular and particle-based structures used as extracellular or intracellular probes in conjunction with different detection modalities and measurement formats. For the different O(2) sensing systems, particular attention is paid to their merits and limitations, analytical performance, general convenience and applicability in specific biological applications. The latter include measurement of O(2) consumption rate, sample oxygenation, sensing of intracellular O(2), metabolic assessment of cells, and O(2) imaging of tissue, vasculature and individual cells. Altogether, this gives the potential user a comprehensive guide for the proper selection of the appropriate optical probe(s) and detection platform to suit their particular biological applications and measurement requirements.
Topics: Animals; Cell Respiration; Luminescent Measurements; Mice; Optical Devices; Oxygen; Rats
PubMed: 22249195
DOI: 10.1007/s00018-011-0914-0 -
The Journal of Neuroscience : the... Jul 2015In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short...
In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 . Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial respiration, leading to mitochondrial depolarization, production of free radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i increases in astrocytes trigger fusion of vesicular compartments containing ATP. Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or targeted astrocyte-specific expression of tetanus toxin light chain (to interfere with vesicular release mechanisms) within the brainstem respiratory rhythm-generating circuits reveals the fundamental physiological role of astroglial oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this mechanism increases breathing activity even in the absence of peripheral chemoreceptor oxygen sensing. These results demonstrate that astrocytes are functionally specialized CNS oxygen sensors tuned for rapid detection of physiological changes in brain oxygenation. Significance statement: Most, if not all, animal cells possess mechanisms that allow them to detect decreases in oxygen availability leading to slow-timescale, adaptive changes in gene expression and cell physiology. To date, only two types of mammalian cells have been demonstrated to be specialized for rapid functional oxygen sensing: glomus cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate breathing when oxygenation of the arterial blood decreases; and pulmonary arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction to limit perfusion of poorly ventilated regions of the lungs. Results of the present study suggest that there is another specialized oxygen-sensitive cell type in the body, the astrocyte, that is tuned for rapid detection of physiological changes in brain oxygenation.
Topics: Animals; Astrocytes; Cell Hypoxia; Cells, Cultured; Chemoreceptor Cells; Immunohistochemistry; Male; Mice; Mice, Knockout; Organ Culture Techniques; Oxygen; Rats; Rats, Sprague-Dawley; Respiratory Physiological Phenomena
PubMed: 26203141
DOI: 10.1523/JNEUROSCI.0045-15.2015 -
Biological Chemistry 2006Sufficient oxygen supply is crucial for the development and physiology of mammalian cells and tissues. When simple diffusion of oxygen becomes inadequate to provide the... (Review)
Review
Sufficient oxygen supply is crucial for the development and physiology of mammalian cells and tissues. When simple diffusion of oxygen becomes inadequate to provide the necessary flow of substrate, evolution has provided cells with tools to detect and respond to hypoxia by upregulating the expression of specific genes, which allows an adaptation to hypoxia-induced stress conditions. The modulation of cell signaling by hypoxia is an emerging area of research that provides insight into the orchestration of cell adaptation to a changing environment. Cell signaling and adaptation processes are often accompanied by rapid and/or chronic remodeling of membrane lipids by activated lipases. This review highlights the bi-directional relation between hypoxia and lipid signaling mechanisms.
Topics: Animals; Cell Hypoxia; Diglycerides; Humans; Lipid Metabolism; Oxygen; Signal Transduction
PubMed: 17081102
DOI: 10.1515/BC.2006.165 -
PloS One 2014Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of...
Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions.
Topics: Biosensing Techniques; Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cell Respiration; Coordination Complexes; Glucose; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Microscopy, Confocal; Mitochondria; Neoplasms; Oxygen; Rotenone
PubMed: 24586439
DOI: 10.1371/journal.pone.0088911 -
Upsala Journal of Medical Sciences Aug 2020Oxygen is of fundamental importance for most living organisms, and the maintenance of oxygen homeostasis is a key physiological challenge for all large animals. Oxygen...
Oxygen is of fundamental importance for most living organisms, and the maintenance of oxygen homeostasis is a key physiological challenge for all large animals. Oxygen deprivation, hypoxia, is a critical component of many human diseases including cancer, heart disease, stroke, vascular disease, and anaemia. The discovery of oxygen sensing provides fundamental knowledge of a stunningly elegant molecular machinery; it also promises development of new therapeutics for serious diseases such as cancer. As a result of their impressive contributions to our understanding of the mechanisms by which cells sense oxygen and signal in hypoxia, Gregg Semenza, Peter Ratcliffe, and William Kaelin were awarded the Nobel Prize in 2019.
Topics: Humans; Neoplasms; Nobel Prize; Oxygen; Tumor Hypoxia
PubMed: 32579052
DOI: 10.1080/03009734.2020.1769231