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1.
Artificial Organelles for Energy Regeneration.
Otrin, L, Kleineberg, C, Caire da Silva, L, Landfester, K, Ivanov, I, Wang, M, Bednarz, C, Sundmacher, K, Vidaković-Koch, T
Advanced biosystems. 2019;(6):e1800323
Abstract
One of the critical steps in sustaining life-mimicking processes in synthetic cells is energy, i.e., adenosine triphosphate (ATP) regeneration. Previous studies have shown that the simple addition of ATP or ATP regeneration systems, which do not regenerate ATP directly from ADP and Pi , have no or only limited success due to accumulation of ATP hydrolysis products. In general, ATP regeneration can be achieved by converting light or chemical energy into ATP, which may also involve redox transformations of cofactors. The present contribution provides an overview of the existing ATP regeneration strategies and the related nicotinamide adenine dinucleotide (NAD+ ) redox cycling, with a focus on compartmentalized systems. Special attention is being paid to those approaches where so-called artificial organelles are developed. They comprise a semipermeable membrane functionalized by biological or man-made components and employ external energy in the form of light or nutrients in order to generate a transmembrane proton gradient, which is further utilized for ATP synthesis.
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2.
ATP, Mg2+, Nuclear Phase Separation, and Genome Accessibility.
Wright, RHG, Le Dily, F, Beato, M
Trends in biochemical sciences. 2019;(7):565-574
Abstract
Misregulation of the processes controlling eukaryotic gene expression can result in disease. Gene expression is influenced by the surrounding chromatin; hence the nuclear environment is also of vital importance. Recently, understanding of chromatin hierarchical folding has increased together with the discovery of membrane-less organelles which are distinct, dynamic liquid droplets that merge and expand within the nucleus. These 'sieve'-like regions may compartmentalize and separate functionally distinct regions of chromatin. This article aims to discuss recent studies on nuclear phase within the context of poly(ADP-ribose), ATP, and Mg2+ levels, and we propose a combinatorial complex role for these molecules in phase separation and genome regulation. We also discuss the implications of this process for gene regulation and discuss possible strategies to test this.
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3.
Cell Fuelling and Metabolic Energy Conservation in Synthetic Cells.
Sikkema, HR, Gaastra, BF, Pols, T, Poolman, B
Chembiochem : a European journal of chemical biology. 2019;(20):2581-2592
Abstract
We are aiming for a blue print for synthesizing (moderately complex) subcellular systems from molecular components and ultimately for constructing life. However, without comprehensive instructions and design principles, we rely on simple reaction routes to operate the essential functions of life. The first forms of synthetic life will not make every building block for polymers de novo according to complex pathways, rather they will be fed with amino acids, fatty acids and nucleotides. Controlled energy supply is crucial for any synthetic cell, no matter how complex. Herein, we describe the simplest pathways for the efficient generation of ATP and electrochemical ion gradients. We have estimated the demand for ATP by polymer synthesis and maintenance processes in small cell-like systems, and we describe circuits to control the need for ATP. We also present fluorescence-based sensors for pH, ionic strength, excluded volume, ATP/ADP, and viscosity, which allow the major physicochemical conditions inside cells to be monitored and tuned.
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4.
A novel method: using an adenosine triphosphate (ATP) luminescence-based assay to rapidly assess the biological stability of drinking water.
Zhang, K, Pan, R, Zhang, T, Xu, J, Zhou, X, Yang, Y
Applied microbiology and biotechnology. 2019;(11):4269-4277
Abstract
The rapid and credible evaluations of the microbial stability of a drinking water distribution system (DWDS) are of great significance for ensuring the safety of drinking water and predicting microbial pollution. Conventional biostability assessment methods mainly focus on bacterial regrowth or evaluation of the level of nutrients that support bacterial regrowth. However, such methods are time-consuming and have many limitations. An adenosine triphosphate (ATP) assay can rapidly measure all active microorganisms and is known to be a useful method to assess the microbial activity of drinking water. The measurement of ATP has been used for more than a decade in the field of drinking water research. This article reviews the application of an ATP luminescence-based method to assess the biostability of drinking water and discusses the feasibility of ATP measurement as a parameter for quickly evaluating this criterion. ATP measurement will help researchers and water managers better monitor the biological stability of drinking water from the source to the consumer's tap. This review covers the: (1) principle and application of the ATP measurement in drinking water quality assessment; (2) comparison of the merits and demerits of several methods for evaluating the biostability of drinking water; (3) discussions on using ATP measurement in evaluating biostability; and (4) improvements in the use of ATP measurement in evaluating biostability. At the end of this review, recommendations were given for better application of the ATP measurement as a parameter for monitoring the microbial quality of drinking water.
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5.
Unidirectional regulation of the F1FO-ATP synthase nanomotor by the ζ pawl-ratchet inhibitor protein of Paracoccus denitrificans and related α-proteobacteria.
Zarco-Zavala, M, Mendoza-Hoffmann, F, García-Trejo, JJ
Biochimica et biophysica acta. Bioenergetics. 2018;(9):762-774
Abstract
The ATP synthase is a reversible nanomotor that gyrates its central rotor clockwise (CW) to synthesize ATP and in counter clockwise (CCW) direction to hydrolyse it. In bacteria and mitochondria, two natural inhibitor proteins, namely the ε and IF1 subunits, prevent the wasteful CCW F1FO-ATPase activity by blocking γ rotation at the αDP/βDP/γ interface of the F1 portion. In Paracoccus denitrificans and related α-proteobacteria, we discovered a different natural F1-ATPase inhibitor named ζ. Here we revise the functional and structural data showing that this novel ζ subunit, although being different to ε and IF1, it also binds to the αDP/βDP/γ interface of the F1 of P. denitrificans. ζ shifts its N-terminal inhibitory domain from an intrinsically disordered protein region (IDPr) to an α-helix when inserted in the αDP/βDP/γ interface. We showed for the first time the key role of a natural ATP synthase inhibitor by the distinctive phenotype of a Δζ knockout mutant in P. denitrificans. ζ blocks exclusively the CCW F1FO-ATPase rotation without affecting the CW-F1FO-ATP synthase turnover, confirming that ζ is important for respiratory bacterial growth by working as a unidirectional pawl-ratchet PdF1FO-ATPase inhibitor, thus preventing the wasteful consumption of cellular ATP. In summary, ζ is a useful model that mimics mitochondrial IF1 but in α-proteobacteria. The structural, functional, and endosymbiotic evolutionary implications of this ζ inhibitor are discussed to shed light on the natural control mechanisms of the three natural inhibitor proteins (ε, ζ, and IF1) of this unique ATP synthase nanomotor, essential for life.
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6.
Role of Ca2+ in Mediating Plant Responses to Extracellular ATP and ADP.
Clark, G, Roux, SJ
International journal of molecular sciences. 2018;(11)
Abstract
Among the most recently discovered chemical regulators of plant growth and development are extracellular nucleotides, especially extracellular ATP (eATP) and extracellular ADP (eADP). Plant cells release ATP into their extracellular matrix under a variety of different circumstances, and this eATP can then function as an agonist that binds to a specific receptor and induces signaling changes, the earliest of which is an increase in the concentration of cytosolic calcium ([Ca2+]cyt). This initial change is then amplified into downstream-signaling changes that include increased levels of reactive oxygen species and nitric oxide, which ultimately lead to major changes in the growth rate, defense responses, and leaf stomatal apertures of plants. This review presents and discusses the evidence that links receptor activation to increased [Ca2+]cyt and, ultimately, to growth and diverse adaptive changes in plant development. It also discusses the evidence that increased [Ca2+]cyt also enhances the activity of apyrase (nucleoside triphosphate diphosphohydrolase) enzymes that function in multiple subcellular locales to hydrolyze ATP and ADP, and thus limit or terminate the effects of these potent regulators.
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7.
Mitochondrial function in Müller cells - Does it matter?
Toft-Kehler, AK, Skytt, DM, Svare, A, Lefevere, E, Van Hove, I, Moons, L, Waagepetersen, HS, Kolko, M
Mitochondrion. 2017;:43-51
Abstract
Growing evidence suggests that mitochondrial dysfunction might play a key role in the pathogenesis of age-related neurodegenerative inner retinal diseases such as diabetic retinopathy and glaucoma. Therefore, the present review provides a perspective on the impact of functional mitochondria in the most predominant glial cells of the retina, the Müller cells. Müller cells span the entire thickness of the neuroretina and are in close proximity to retinal cells including the retinal neurons that provides visual signaling to the brain. Among multiple functions, Müller cells are responsible for the removal of neurotransmitters, buffering potassium, and providing neurons with essential metabolites. Thus, Müller cells are responsible for a stable metabolic dialogue in the inner retina and their crucial role in supporting retinal neurons is indisputable. Müller cell functions require considerable energy production and previous literature has primarily emphasized glycolysis as the main energy provider. However, recent studies highlight the need of mitochondrial ATP production to upheld Müller cell functions. Therefore, the present review aims to provide an overview of the current evidence on the impact of mitochondrial functions in Müller cells.
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8.
Mitochondria: a central target for sex differences in pathologies.
Ventura-Clapier, R, Moulin, M, Piquereau, J, Lemaire, C, Mericskay, M, Veksler, V, Garnier, A
Clinical science (London, England : 1979). 2017;(9):803-822
Abstract
It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy. It appears that mitochondria are the place of marked sexual dimorphism involving mainly oxidative capacities, calcium handling, and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial function and biogenesis. Mutations in genes encoding mitochondrial proteins are the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction is also an important parameter for a large panel of pathologies including neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs), metabolic disorders, neuropathies, renal dysfunction etc. Many of these pathologies present sex/gender specificity. Here we review the sexual dimorphism of mitochondria from different tissues and how this dimorphism takes part in the sex specificity of important pathologies mainly CVDs and neurological disorders.
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9.
Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development.
Wilde, L, Roche, M, Domingo-Vidal, M, Tanson, K, Philp, N, Curry, J, Martinez-Outschoorn, U
Seminars in oncology. 2017;(3):198-203
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Abstract
Glucose is a key metabolite used by cancer cells to generate ATP, maintain redox state and create biomass. Glucose can be catabolized to lactate in the cytoplasm, which is termed glycolysis, or alternatively can be catabolized to carbon dioxide and water in the mitochondria via oxidative phosphorylation. Metabolic heterogeneity exists in a subset of human tumors, with some cells maintaining a glycolytic phenotype while others predominantly utilize oxidative phosphorylation. Cells within tumors interact metabolically with transfer of catabolites from supporting stromal cells to adjacent cancer cells. The Reverse Warburg Effect describes when glycolysis in the cancer-associated stroma metabolically supports adjacent cancer cells. This catabolite transfer, which induces stromal-cancer metabolic coupling, allows cancer cells to generate ATP, increase proliferation, and reduce cell death. Catabolites implicated in metabolic coupling include the monocarboxylates lactate, pyruvate, and ketone bodies. Monocarboxylate transporters (MCT) are critically necessary for release and uptake of these catabolites. MCT4 is involved in the release of monocarboxylates from cells, is regulated by catabolic transcription factors such as hypoxia inducible factor 1 alpha (HIF1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and is highly expressed in cancer-associated fibroblasts. Conversely, MCT1 is predominantly involved in the uptake of these catabolites and is highly expressed in a subgroup of cancer cells. MYC and TIGAR, which are genes involved in cellular proliferation and anabolism, are inducers of MCT1. Profiling human tumors on the basis of an altered redox balance and intra-tumoral metabolic interactions may have important biomarker and therapeutic implications. Alterations in the redox state and mitochondrial function of cells can induce metabolic coupling. Hence, there is interest in redox and metabolic modulators as anticancer agents. Also, markers of metabolic coupling have been associated with poor outcomes in numerous human malignancies and may be useful prognostic and predictive biomarkers.
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10.
The Role of Extracellular Adenosine Triphosphate in Ischemic Organ Injury.
Zhao, H, Kilgas, S, Alam, A, Eguchi, S, Ma, D
Critical care medicine. 2016;(5):1000-12
Abstract
OBJECTIVES Ischemic tissue injury contributes to significant morbidity and mortality and is implicated in a range of pathologic conditions, including but not limited to myocardial infarction, ischemic stroke, and acute kidney injury. The associated reperfusion phase is responsible for the activation of the innate and adaptive immune system, further accentuating inflammation. Adenosine triphosphate molecule has been implicated in various ischemic conditions, including stroke and myocardial infarction. STUDY SELECTION Adenosine triphosphate is a well-defined intracellular energy transfer and is commonly referred to as the body's "energy currency." However, Laboratory studies have demonstrated that extracellular adenosine triphosphate has the ability to initiate inflammation and is therefore referred to as a damage-associated molecular pattern. Purinergic receptors-dependent signaling, proinflammatory cytokine release, increased Ca influx into cells, and subsequent apoptosis have been shown to form a common underlying extracellular adenosine triphosphate molecular mechanism in ischemic organ injury. CONCLUSIONS In this review, we aim to discuss the molecular mechanisms behind adenosine triphosphate-mediated ischemic tissue injury and evaluate the role of extracellular adenosine triphosphate in ischemic injury in specific organs, in order to provide a greater understanding of the pathophysiology of this complex process. We also appraise potential future therapeutic strategies to limit damage in various organs, including the heart, brain, kidneys, and lungs.