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The Journal of Biological Chemistry Oct 2015Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that... (Review)
Review
Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal-driven motions that animate the complete MMR mechanism.
Topics: Adenosine Triphosphate; Animals; DNA; DNA Mismatch Repair; DNA Repair Enzymes; Humans; Nuclear Proteins
PubMed: 26354434
DOI: 10.1074/jbc.R115.660142 -
Journal of Lipid Research Jun 2016Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and... (Review)
Review
Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and anabolic processes in mammals. SCFAs are mostly generated by colonic bacteria and are predominantly metabolized by enterocytes and liver, whereas MCFAs arise mostly from dietary triglycerides, among them milk and dairy products. A common feature of SCFAs and MCFAs is their carnitine-independent uptake and intramitochondrial activation to acyl-CoA thioesters. Contrary to long-chain fatty acids, the cellular metabolism of SCFAs and MCFAs depends to a lesser extent on fatty acid-binding proteins. SCFAs and MCFAs modulate tissue metabolism of carbohydrates and lipids, as manifested by a mostly inhibitory effect on glycolysis and stimulation of lipogenesis or gluconeogenesis. SCFAs and MCFAs exert no or only weak protonophoric and lytic activities in mitochondria and do not significantly impair the electron transport in the respiratory chain. SCFAs and MCFAs modulate mitochondrial energy production by two mechanisms: they provide reducing equivalents to the respiratory chain and partly decrease efficacy of oxidative ATP synthesis.
Topics: Acyl Coenzyme A; Adenosine Triphosphate; Carnitine; Energy Metabolism; Fatty Acids; Humans; Mitochondria; Oxidation-Reduction; Triglycerides
PubMed: 27080715
DOI: 10.1194/jlr.R067629 -
Targeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications.Seminars in Cancer Biology Nov 2022Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought... (Review)
Review
Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.
Topics: Humans; Oxidative Phosphorylation; Electron Transport; Glycolysis; Neoplasms; Adenosine Triphosphate
PubMed: 35122973
DOI: 10.1016/j.semcancer.2022.02.002 -
Frontiers in Endocrinology 2022Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an... (Review)
Review
Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an extracellular signal that activates purinergic plasma membrane receptors of the P2 family. P2 receptors are divided into two types: ATP-gated nonselective cation channels (P2X) and G protein-coupled receptors (P2Y), the latter being activated by a broad range of purine and pyrimidine nucleotides (ATP, ADP, UTP, and UDP, among others). Purinergic signaling mechanisms are involved in numerous physiological events and pathophysiological conditions. Here, we address the growing body of evidence implicating purinergic signaling in male reproductive system functions. The life-long generation of fertile male germ cells is a highly complex, yet mechanistically poorly understood process. Given the relatively sparse innervation of the testis, spermatogenesis relies on both endocrine control and multi-directional paracrine communication. Therefore, a detailed understanding of such paracrine messengers, including ATP, is crucial to gain mechanistic insight into male reproduction..
Topics: Adenosine Triphosphate; Endocrine System; Humans; Male; Receptors, Purinergic; Signal Transduction; Spermatogenesis
PubMed: 35480481
DOI: 10.3389/fendo.2022.867011 -
The EMBO Journal Jul 2021While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor... (Review)
Review
While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of cis- and trans-regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Topics: Adenosine Triphosphate; Animals; Humans; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 34121201
DOI: 10.15252/embj.2021108130 -
Cold Spring Harbor Perspectives in... Mar 2021
Review
Topics: Adenosine Triphosphate; Archaea; Calcium; Citric Acid Cycle; Glucose; Glycolysis; Homeostasis; Mitochondria; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Proteobacteria; Reactive Oxygen Species; Symbiosis
PubMed: 33649187
DOI: 10.1101/cshperspect.a040543 -
Cold Spring Harbor Perspectives in... May 2018Animals possess a remarkable ability to perform physical activity over a wide range of workloads and durations, reflecting both the inherent efficiency and large reserve... (Review)
Review
Animals possess a remarkable ability to perform physical activity over a wide range of workloads and durations, reflecting both the inherent efficiency and large reserve capacity of energy transfer systems. Deciphering how different organ/physiological systems respond to the acute and chronic demands of exercise depends on a foundational understanding of the redox and bioenergetic principles that underlie the flow of electrons in living systems and its coupling to ATP synthesis. The purpose of this review is to set the stage to cover (1) the thermodynamic driving forces responsible for generating and maintaining the energy charge that establishes and sustains life for cells, and (2) how cellular energy transfer systems respond to changes in energy demand to ensure energy charge is preserved.
Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Exercise; Humans; Oxidation-Reduction
PubMed: 28490536
DOI: 10.1101/cshperspect.a029678 -
The Biological Bulletin Aug 2016Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence... (Review)
Review
Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.
Topics: Adenosine Triphosphate; Animals; Aptamers, Nucleotide; Bioluminescence Resonance Energy Transfer Techniques; Fluorescence Resonance Energy Transfer; Microscopy; Molecular Imaging; Molecular Probes; Optical Imaging
PubMed: 27638696
DOI: 10.1086/689592 -
Purinergic Signalling Mar 2023Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension... (Review)
Review
Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. AR, AR, AR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.
Topics: Humans; Endothelial Cells; Receptors, Purinergic; Synaptic Transmission; Signal Transduction; Hypertension; Adenosine Triphosphate
PubMed: 35181831
DOI: 10.1007/s11302-022-09852-8 -
Purinergic Signalling Sep 2021Purinergic signaling plays a pivotal role in physiological processes and pathological conditions. Over the past decades, conventional pharmacological, biochemical, and... (Review)
Review
Purinergic signaling plays a pivotal role in physiological processes and pathological conditions. Over the past decades, conventional pharmacological, biochemical, and molecular biology techniques have been utilized to investigate purinergic signaling cascades. However, none of them is capable of spatially and temporally manipulating purinergic signaling cascades. Currently, optical approaches, including optopharmacology and optogenetic, enable controlling purinergic signaling with low invasiveness and high spatiotemporal precision. In this mini-review, we discuss optical approaches for controlling purinergic signaling and their applications in basic and translational science.
Topics: Adenosine Triphosphate; Animals; Humans; Optogenetics; Photolysis; Receptors, Purinergic; Signal Transduction
PubMed: 34156578
DOI: 10.1007/s11302-021-09799-2