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Physiological Reviews Oct 2015Aquaporins are membrane channels that facilitate the transport of water and small neutral molecules across biological membranes of most living organisms. In plants,... (Review)
Review
Aquaporins are membrane channels that facilitate the transport of water and small neutral molecules across biological membranes of most living organisms. In plants, aquaporins occur as multiple isoforms reflecting a high diversity of cellular localizations, transport selectivity, and regulation properties. Plant aquaporins are localized in the plasma membrane, endoplasmic reticulum, vacuoles, plastids and, in some species, in membrane compartments interacting with symbiotic organisms. Plant aquaporins can transport various physiological substrates in addition to water. Of particular relevance for plants is the transport of dissolved gases such as carbon dioxide and ammonia or metalloids such as boron and silicon. Structure-function studies are developed to address the molecular and cellular mechanisms of plant aquaporin gating and subcellular trafficking. Phosphorylation plays a central role in these two processes. These mechanisms allow aquaporin regulation in response to signaling intermediates such as cytosolic pH and calcium, and reactive oxygen species. Combined genetic and physiological approaches are now integrating this knowledge, showing that aquaporins play key roles in hydraulic regulation in roots and leaves, during drought but also in response to stimuli as diverse as flooding, nutrient availability, temperature, or light. A general hydraulic control of plant tissue expansion by aquaporins is emerging, and their role in key developmental processes (seed germination, emergence of lateral roots) has been established. Plants with genetically altered aquaporin functions are now tested for their ability to improve plant tolerance to stresses. In conclusion, research on aquaporins delineates ever expanding fields in plant integrative biology thereby establishing their crucial role in plants.
Topics: Animals; Aquaporins; Biological Transport; Humans; Hydrogen-Ion Concentration; Plants; Stress, Physiological
PubMed: 26336033
DOI: 10.1152/physrev.00008.2015 -
Free Radical Biology & Medicine Mar 2019Many past and recent advances in the field of iron metabolism have relied upon the discovery of divalent metal transporter 1, DMT1 in 1997. DMT1 is the major iron... (Review)
Review
Many past and recent advances in the field of iron metabolism have relied upon the discovery of divalent metal transporter 1, DMT1 in 1997. DMT1 is the major iron transporter and contributes non-heme iron uptake in most types of cell. Each DMT1 isoform exhibits different expression patterns in cell-type specificity and distinct subcellular distribution, which enables cells to uptake both transferrin-bound and non-transferrin-bound irons efficiently. DMT1 expression is regulated by iron through the translational and degradation pathways to ensure iron homeostasis. It is considered that mammalian iron transporters including DMT1 cannot transport ferric iron but ferrous iron. Being reduced to ferrous state is likely to damage cells and tissues through the production of reactive oxygen species. Recently, iron chaperones have been identified, which can provide an answer to how ferrous iron is transported safely in cytosol. We summarize DMT1 expression depending on the types of cell or tissue and the function and mechanism of one of the iron chaperones, PCBP2.
Topics: Animals; Biological Transport; Cation Transport Proteins; Gene Expression Regulation; Humans; Ion Transport; Iron; Molecular Chaperones; Protein Isoforms; RNA-Binding Proteins; Transferrin
PubMed: 30055235
DOI: 10.1016/j.freeradbiomed.2018.07.020 -
Current Biology : CB Nov 2017Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much... (Review)
Review
Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much larger suite of functions and that these functions can vary substantially among diverse eukaryotic lineages. Despite this diversity, all mitochondria derive from a common ancestral organelle that originated from the integration of an endosymbiotic alphaproteobacterium into a host cell related to Asgard Archaea. The transition from endosymbiotic bacterium to permanent organelle entailed a massive number of evolutionary changes including the origins of hundreds of new genes and a protein import system, insertion of membrane transporters, integration of metabolism and reproduction, genome reduction, endosymbiotic gene transfer, lateral gene transfer and the retargeting of proteins. These changes occurred incrementally as the endosymbiont and the host became integrated. Although many insights into this transition have been gained, controversy persists regarding the nature of the original endosymbiont, its initial interactions with the host and the timing of its integration relative to the origin of other features of eukaryote cells. Since the establishment of the organelle, proteins have been gained, lost, transferred and retargeted as mitochondria have specialized into the spectrum of functional types seen across the eukaryotic tree of life.
Topics: Adenosine Triphosphate; Alphaproteobacteria; Biological Evolution; Eukaryotic Cells; Genome, Mitochondrial; Membrane Transport Proteins; Mitochondria; Protein Transport; Symbiosis
PubMed: 29112874
DOI: 10.1016/j.cub.2017.09.015 -
International Journal of Molecular... Jul 2019The mammalian mitochondrial electron transport chain (ETC) includes complexes I‑IV, as well as the electron transporters ubiquinone and cytochrome c. There are two...
The mammalian mitochondrial electron transport chain (ETC) includes complexes I‑IV, as well as the electron transporters ubiquinone and cytochrome c. There are two electron transport pathways in the ETC: Complex I/III/IV, with NADH as the substrate and complex II/III/IV, with succinic acid as the substrate. The electron flow is coupled with the generation of a proton gradient across the inner membrane and the energy accumulated in the proton gradient is used by complex V (ATP synthase) to produce ATP. The first part of this review briefly introduces the structure and function of complexes I‑IV and ATP synthase, including the specific electron transfer process in each complex. Some electrons are directly transferred to O2 to generate reactive oxygen species (ROS) in the ETC. The second part of this review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS. As signaling molecules, ROS play an important role in cell proliferation, hypoxia adaptation and cell fate determination, but excessive ROS can cause irreversible cell damage and even cell death. The occurrence and development of a number of diseases are closely related to ROS overproduction. Finally, proton leak and uncoupling proteins (UCPS) are discussed. Proton leak consists of basal proton leak and induced proton leak. Induced proton leak is precisely regulated and induced by UCPs. A total of five UCPs (UCP1‑5) have been identified in mammalian cells. UCP1 mainly plays a role in the maintenance of body temperature in a cold environment through non‑shivering thermogenesis. The core role of UCP2‑5 is to reduce oxidative stress under certain conditions, therefore exerting cytoprotective effects. All diseases involving oxidative stress are associated with UCPs.
Topics: Animals; Cell Hypoxia; Cell Proliferation; Electron Transport Chain Complex Proteins; Humans; Mitochondria; Mitochondrial Uncoupling Proteins; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Thermogenesis
PubMed: 31115493
DOI: 10.3892/ijmm.2019.4188 -
Nature Dec 2020Mitochondria require nicotinamide adenine dinucleotide (NAD) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction....
Mitochondria require nicotinamide adenine dinucleotide (NAD) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD transporters have been identified in yeast and plants, but their existence in mammals remains controversial. Here we demonstrate that mammalian mitochondria can take up intact NAD, and identify SLC25A51 (also known as MCART1)-an essential mitochondrial protein of previously unknown function-as a mammalian mitochondrial NAD transporter. Loss of SLC25A51 decreases mitochondrial-but not whole-cell-NAD content, impairs mitochondrial respiration, and blocks the uptake of NAD into isolated mitochondria. Conversely, overexpression of SLC25A51 or SLC25A52 (a nearly identical paralogue of SLC25A51) increases mitochondrial NAD levels and restores NAD uptake into yeast mitochondria lacking endogenous NAD transporters. Together, these findings identify SLC25A51 as a mammalian transporter capable of importing NAD into mitochondria.
Topics: Animals; Biological Transport; Cell Line; Cell Respiration; Genetic Complementation Test; Humans; Mice; Mitochondria; Mitochondrial Proteins; NAD; Nucleotide Transport Proteins; Organic Cation Transport Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 32906142
DOI: 10.1038/s41586-020-2741-7 -
Oxidative Medicine and Cellular... 2018
Topics: Alzheimer Disease; Biological Transport; Cardiovascular Diseases; Humans; Membrane Transport Proteins; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species
PubMed: 30008987
DOI: 10.1155/2018/9625213 -
Current Pharmaceutical Design 2022Blood flow enables the delivery of oxygen and nutrients to the different tissues of the human body. Drugs follow the same route as oxygen and nutrients; thus, drug...
Blood flow enables the delivery of oxygen and nutrients to the different tissues of the human body. Drugs follow the same route as oxygen and nutrients; thus, drug concentrations in tissues are highly dependent on the blood flow fraction delivered. Although the free drug concentration in blood correlates with pharmacodynamics, the pharmacodynamics of a drug is primarily commanded by the drug concentrations in the aqueous spaces of bodily tissues. However, the concentrations of the drug are not homogeneous throughout the tissues, and they rarely reflect the free drug concentration in the blood. This heterogeneity is due to differences in the blood flow fraction delivered to the tissues and membrane transporters, efflux pumps, and metabolic enzymes. The rate of drug elimination from the body (systemic elimination) depends more on the driving force of drug elimination than on the free concentration of the drug at the site from which the drug is being eliminated. In fact, the actual free drug concentration in the tissues results from the balance between the input and output rates. In the present paper, we develop a theoretical concept regarding solute partition between intravascular and extravascular spaces; discuss experimental research on aqueous/non-aqueous solute partitioning and clinical research on microdialysis; present hypotheses to predict in-vivo elimination using parameters of in-vitro metabolism.
Topics: Biological Transport; Humans; Membrane Transport Proteins; Oxygen; Solutions; Tissue Distribution
PubMed: 35466869
DOI: 10.2174/1381612828666220422091159 -
Science Translational Medicine Jun 2016α-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be...
α-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be related. Mitochondrial dysfunction leads to accumulation and oligomerization of α-synuclein, and increased levels of α-synuclein cause mitochondrial impairment, but the basis for this bidirectional interaction remains obscure. We now report that certain posttranslationally modified species of α-synuclein bind with high affinity to the TOM20 (translocase of the outer membrane 20) presequence receptor of the mitochondrial protein import machinery. This binding prevented the interaction of TOM20 with its co-receptor, TOM22, and impaired mitochondrial protein import. Consequently, there were deficient mitochondrial respiration, enhanced production of reactive oxygen species, and loss of mitochondrial membrane potential. Examination of postmortem brain tissue from PD patients revealed an aberrant α-synuclein-TOM20 interaction in nigrostriatal dopaminergic neurons that was associated with loss of imported mitochondrial proteins, thereby confirming this pathogenic process in the human disease. Modest knockdown of endogenous α-synuclein was sufficient to maintain mitochondrial protein import in an in vivo model of PD. Furthermore, in in vitro systems, overexpression of TOM20 or a mitochondrial targeting signal peptide had beneficial effects and preserved mitochondrial protein import. This study characterizes a pathogenic mechanism in PD, identifies toxic species of wild-type α-synuclein, and reveals potential new therapeutic strategies for neuroprotection.
Topics: Animals; Membrane Transport Proteins; Mitochondria; Mitochondrial Precursor Protein Import Complex Proteins; Mitochondrial Proteins; Parkinson Disease; Protein Binding; Protein Transport; Rats; Rats, Mutant Strains; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; alpha-Synuclein
PubMed: 27280685
DOI: 10.1126/scitranslmed.aaf3634 -
Annual Review of Biochemistry Jun 2020Complex carbohydrates are essential for many biological processes, from protein quality control to cell recognition, energy storage, and cell wall formation. Many of... (Review)
Review
Complex carbohydrates are essential for many biological processes, from protein quality control to cell recognition, energy storage, and cell wall formation. Many of these processes are performed in topologically extracellular compartments or on the cell surface; hence, diverse secretion systems evolved to transport the hydrophilic molecules to their sites of action. Polyprenyl lipids serve as ubiquitous anchors and facilitators of these transport processes. Here, we summarize and compare bacterial biosynthesis pathways relying on the recognition and transport of lipid-linked complex carbohydrates. In particular, we compare transporters implicated in O antigen and capsular polysaccharide biosyntheses with those facilitating teichoic acid and -linked glycan transport. Further, we discuss recent insights into the generation, recognition, and recycling of polyprenyl lipids.
Topics: ATP-Binding Cassette Transporters; Bacillus subtilis; Bacterial Proteins; Biological Transport; Carbon-Oxygen Ligases; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Glycolipids; Glycosyltransferases; Klebsiella pneumoniae; Membrane Transport Proteins; Models, Molecular; O Antigens; Polyprenols; Protein Structure, Secondary; Pseudomonas aeruginosa; Teichoic Acids; Transferases (Other Substituted Phosphate Groups)
PubMed: 32569526
DOI: 10.1146/annurev-biochem-011520-104707 -
Current Opinion in Chemical Biology Apr 2020Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in... (Review)
Review
Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in stressful environments. This review summarizes new aspects of regulatory strategies to control intracellular Mn levels and gives an overview of several newly identified families of bacterial Mn transporters. Recent illustrative examples of advances in quantification of intracellular Mn pools and characterization of the effects of Mn perturbations are highlighted. These discoveries help define mechanisms of Mn selectivity and toxicity and could enable new strategies to combat pathogenic bacteria and promote growth of desirable bacteria.
Topics: Amino Acid Sequence; Bacteria; Bacterial Proteins; Cell Membrane Permeability; Gene Expression Regulation, Bacterial; Homeostasis; Manganese; Membrane Transport Proteins; Mutation; Reactive Oxygen Species; Riboswitch; Substrate Specificity; Superoxide Dismutase; Transcription Factors
PubMed: 32086169
DOI: 10.1016/j.cbpa.2020.01.003