-
The Journal of Biological Chemistry Sep 2023The hydrolysis of ATP is the primary source of metabolic energy for eukaryotic cells. Under physiological conditions, cells generally produce more than sufficient levels... (Review)
Review
The hydrolysis of ATP is the primary source of metabolic energy for eukaryotic cells. Under physiological conditions, cells generally produce more than sufficient levels of ATP to fuel the active biological processes necessary to maintain homeostasis. However, mechanisms underpinning the distribution of ATP to subcellular microenvironments with high local demand remain poorly understood. Intracellular distribution of ATP in normal physiological conditions has been proposed to rely on passive diffusion across concentration gradients generated by ATP producing systems such as the mitochondria and the glycolytic pathway. However, subcellular microenvironments can develop with ATP deficiency due to increases in local ATP consumption. Alternatively, ATP production can be reduced during bioenergetic stress during hypoxia. Mammalian cells therefore need to have the capacity to alter their metabolism and energy distribution strategies to compensate for local ATP deficits while also controlling ATP production. It is highly likely that satisfying the bioenergetic requirements of the cell involves the regulated distribution of ATP producing systems to areas of high ATP demand within the cell. Recently, the distribution (both spatially and temporally) of ATP-producing systems has become an area of intense investigation. Here, we review what is known (and unknown) about intracellular energy production and distribution and explore potential mechanisms through which this targeted distribution can be altered in hypoxia, with the aim of stimulating investigation in this important, yet poorly understood field of research.
Topics: Animals; Humans; Adenosine Triphosphate; Energy Metabolism; Mitochondria; Cell Hypoxia; Adaptation, Physiological
PubMed: 37507013
DOI: 10.1016/j.jbc.2023.105103 -
Biological Chemistry Sep 2023ATP is an important small molecule that appears at outstandingly high concentration within the cellular medium. Apart from its use as a source of energy and a... (Review)
Review
ATP is an important small molecule that appears at outstandingly high concentration within the cellular medium. Apart from its use as a source of energy and a metabolite, there is increasing evidence for important functions as a cosolute for biomolecular processes. Owned to its solubilizing kosmotropic triphosphate and hydrophobic adenine moieties, ATP is a versatile cosolute that can interact with biomolecules in various ways. We here use three models to categorize these interactions and apply them to review recent studies. We focus on the impact of ATP on biomolecular solubility, folding stability and phase transitions. This leads us to possible implications and therapeutic interventions in neurodegenerative diseases.
Topics: Solubility; Adenosine Triphosphate
PubMed: 37656203
DOI: 10.1515/hsz-2023-0202 -
Clinica Chimica Acta; International... Jan 2019Glycolytic enzymes are among the most frequently identified proteins in proteomics of exosomes/extracellular vesicles. This review brings up the possibility that... (Review)
Review
Glycolytic enzymes are among the most frequently identified proteins in proteomics of exosomes/extracellular vesicles. This review brings up the possibility that exosomes/extracellular vesicles during their life-time in bodily fluids power important energy-consuming functions by glycolytic conversion of glucose or fructose into ATP. It was seen that prostasomes (exosomes of the prostate) could produce ATP by glycolysis and that the produced ATP quickly was consumed by adjacent prostasomal ATPases. The glycolytic ATP production appeared to be coupled to self-sustaining energy requirements. It will also be discussed how a failure in this machinery (lowered activity of ATPases) with a resultant polluting leakage of extracellular ATP could affect cancer development.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Energy Metabolism; Extracellular Vesicles; Humans; Neoplasms
PubMed: 30395864
DOI: 10.1016/j.cca.2018.10.044 -
FEBS Letters Sep 2015The chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the... (Review)
Review
The chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein. Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structure-function relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements.
Topics: Adenosine Triphosphate; Allosteric Regulation; Chaperonins; Cluster Analysis; Models, Molecular; Molecular Dynamics Simulation; Pliability; Protein Binding; Protein Conformation; Protein Folding
PubMed: 26140986
DOI: 10.1016/j.febslet.2015.06.019 -
Cells Oct 2022Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells... (Review)
Review
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. Metabolites not only provide stem/progenitor cells with nutrients for ATP and building block generation but are also utilized for protein modification and epigenetic regulation to maintain cellular characteristics. In recent years, the metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods. In this review, we first present the advantages and disadvantages of the current approaches applicable to the metabolic analysis of tissue stem/progenitor cells, including HSCs and HPCs. In the second half, we discuss the characteristics and regulatory mechanisms of HSC metabolism, including the decoupling of ATP production by glycolysis and mitochondria. These technologies and findings have the potential to advance stem cell biology and engineering from a metabolic perspective and to establish therapeutic approaches.
Topics: Epigenesis, Genetic; Hematopoietic Stem Cells; Bone Marrow; Glycolysis; Adenosine Triphosphate
PubMed: 36291056
DOI: 10.3390/cells11203189 -
Current Opinion in Chemical Biology Dec 2018The bacterial enzyme nitrogenase achieves the reduction of dinitrogen (N) to ammonia (NH) utilizing electrons, protons, and energy from the hydrolysis of ATP. Building... (Review)
Review
The bacterial enzyme nitrogenase achieves the reduction of dinitrogen (N) to ammonia (NH) utilizing electrons, protons, and energy from the hydrolysis of ATP. Building on earlier foundational knowledge, recent studies provide molecular-level details on how the energy of ATP hydrolysis is utilized, the sequencing of multiple electron transfer events, and the nature of energy transduction across this large protein complex. Here, we review the state of knowledge about energy transduction in nitrogenase.
Topics: Adenosine Triphosphate; Bacteria; Electron Transport; Hydrolysis; Models, Biological; Models, Chemical; Nitrogen; Nitrogenase; Oxidation-Reduction
PubMed: 30205289
DOI: 10.1016/j.cbpa.2018.08.011 -
Trends in Cancer Dec 2017Until recently, the dual roles of mitochondria in ATP production (bioenergetics) and apoptosis (cell life/death decision) were thought to be separate. New evidence... (Review)
Review
Until recently, the dual roles of mitochondria in ATP production (bioenergetics) and apoptosis (cell life/death decision) were thought to be separate. New evidence points to a more intimate link between these two functions, mediated by the remodeling of the mitochondrial ultrastructure during apoptosis. While most of the key molecular players that regulate this process have been identified (primarily membrane proteins), the exact mechanisms by which they function are not yet understood. Because resistance to apoptosis is a hallmark of cancer, and because ultimately all chemotherapies are believed to result directly or indirectly in induction of apoptosis, a better understanding of the biophysical processes involved may lead to new avenues for therapy.
Topics: Adenosine Triphosphate; Apoptosis; Energy Metabolism; Humans; Mitochondria; Mitochondrial Membranes; Neoplasms
PubMed: 29198441
DOI: 10.1016/j.trecan.2017.10.006 -
Purinergic Signalling Jun 2022Historically, mainly by the work of Robert Berne, extracellular adenosine was the first purine compound recognized as an important signaling molecule linking energy... (Review)
Review
Historically, mainly by the work of Robert Berne, extracellular adenosine was the first purine compound recognized as an important signaling molecule linking energy metabolism to function by acting on membrane bound receptors. Geoffrey Burnstock by his vision and endurance pioneered the idea that cells release ATP that also acts as an extracellular signaling molecule under many physiological and pathophysiological circumstances. Only later, it was appreciated that extracellular ATP and adenosine are metabolically linked by the activity of several ectoenzymes which critically determine the concentrations of these purines at their respective receptors. In this brief review, I will report some personal recollections on Geoffrey Burnstock and his impressive personality. In addition, I will give a brief overview on our present knowledge of extracellular purine metabolism and its control and will address some still open issues.
Topics: Adenosine; Adenosine Triphosphate; Energy Metabolism; Receptors, Purinergic; Signal Transduction
PubMed: 35522386
DOI: 10.1007/s11302-022-09862-6 -
Purinergic Signalling Sep 2021Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor... (Review)
Review
Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.
Topics: Adenosine Triphosphate; Animals; Autocrine Communication; Humans; Neoplasms; Paracrine Communication; Receptors, Purinergic; Signal Transduction
PubMed: 33982134
DOI: 10.1007/s11302-021-09785-8 -
Biochemistry. Biokhimiia Oct 2023Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of... (Review)
Review
Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell. This analytical review gives the history of the cable theory, lists unsolved critical problems, describes the restructuring of the mitochondrial network and the role of oxidative stress in this process. In addition to the already proven functioning of extended mitochondrial structures as electrical cables, a number of additional functions are proposed, in particular, the hypothesis is put forth that mitochondrial networks maintain the redox potential in the cellular volume, which may vary depending on the physiological state, as a result of changes in the three-dimensional organization of the mitochondrial network (fragmentation/fission-fusion). A number of pathologies accompanied by a violation of the redox status and the participation of mitochondria in them are considered.
Topics: Mitochondria; Oxidation-Reduction; Oxidative Stress; Adenosine Triphosphate
PubMed: 38105027
DOI: 10.1134/S0006297923100140