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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 -
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 -
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 -
Biological Research Jan 2018Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein (MIP) superfamily that play an important role in plant water relations. The main role of... (Review)
Review
Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein (MIP) superfamily that play an important role in plant water relations. The main role of aquaporins in plants is transport of water and other small neutral molecules across cellular biological membranes. AQPs have remarkable features to provide an efficient and often, specific water flow and enable them to transport water into and out of the cells along the water potential gradient. Plant AQPs are classified into five main subfamilies including the plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26 like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and X intrinsic proteins (XIPs). AQPs are localized in the cell membranes and are found in all living cells. However, most of the AQPs that have been described in plants are localized to the tonoplast and plasma membranes. Regulation of AQP activity and gene expression, are also considered as a part of the adaptation mechanisms to stress conditions and rely on complex processes and signaling pathways as well as complex transcriptional, translational and posttranscriptional factors. Gating of AQPs through different mechanisms, such as phosphorylation, tetramerization, pH, cations, reactive oxygen species, phytohormones and other chemical agents, may play a key role in plant responses to environmental stresses by maintaining the uptake and movement of water in the plant body.
Topics: Aquaporins; Biological Transport; Gene Expression; Plants; Stress, Physiological
PubMed: 29338771
DOI: 10.1186/s40659-018-0152-0 -
Pediatric Critical Care Medicine : a... Jul 2011Alterations of hemodynamics and oxygen transport balance are very common scenarios in the pediatric intensive care unit (PICU), and these alterations are as...
Alterations of hemodynamics and oxygen transport balance are very common scenarios in the pediatric intensive care unit (PICU), and these alterations are as heterogeneous and diverse in nature as are the patient populations that typically exist in the PICU. Accordingly, the PICU perspective on monitoring of hemodynamics and oxygen transport balance in critically ill children must be understood in this context of heterogeneity and diversity. We provide an interpretation of the evidence supporting various monitoring strategies as presented in the The Pediatric Cardiac Intensive Care Society Evidence Based Review and Consensus Statement on Monitoring of Hemodynamics and Oxygen Transport Balance from a Pediatric Intensive Care perspective.
Topics: Biological Transport; Child, Preschool; Hemodynamics; Humans; Infant; Intensive Care Units, Pediatric; Monitoring, Physiologic; Oxygen; Oxygen Consumption; Shock
PubMed: 21857798
DOI: 10.1097/PCC.0b013e3182211c60 -
Biochimica Et Biophysica Acta Oct 2016Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca(2+), regulation of metabolite transport by extramitochondrial Ca(2+)... (Review)
Review
Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca(2+), regulation of metabolite transport by extramitochondrial Ca(2+) represents an alternative Ca(2+)-dependent mechanism to regulate mitochondrial function. The Ca(2+) regulated mitochondrial transporters (CaMCs) are well suited for that role, as they contain long N-terminal extensions harboring EF-hand Ca(2+) binding domains facing the intermembrane space. They fall in two groups, the aspartate/glutamate exchangers, AGCs, major components of the NADH malate aspartate shuttle (MAS) and urea cycle, and the ATP-Mg(2+)/Pi exchangers or short CaMCs (APCs or SCaMCs). The AGCs are activated by relatively low Ca(2+) levels only slightly higher than resting Ca(2+), whereas all SCaMCs studied so far require strong Ca(2+) signals, above micromolar, for activation. In addition, AGCs are not strictly Ca(2+) dependent, being active even in Ca(2+)-free conditions. Thus, AGCs are well suited to respond to small Ca(2+) signals and that do not reach mitochondria. In contrast, ATP-Mg(2+)/Pi carriers are inactive in Ca(2+) free conditions and activation requires Ca(2+) signals that will also activate the calcium uniporter (MCU). By changing the net content of adenine nucleotides of the matrix upon activation, SCaMCs regulate the activity of the permeability transition pore, and the Ca(2+) retention capacity of mitochondria (CRC), two functions synergizing with those of the MCU. The different Ca(2+) activation properties of the two CaMCs are discussed in relation to their newly obtained structures. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Topics: Animals; Antiporters; Arabidopsis Proteins; Biological Transport, Active; Calcium; Calcium Signaling; Calcium-Binding Proteins; Cell Respiration; Humans; Ion Transport; Mammals; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes; Mitochondrial Proteins; Models, Molecular; Organic Anion Transporters; Protein Conformation; Saccharomyces cerevisiae Proteins
PubMed: 27033520
DOI: 10.1016/j.bbamcr.2016.03.024 -
Biochimica Et Biophysica Acta Oct 2016In this review we discuss the structure and functions of the aspartate/glutamate carriers (AGC1-aralar and AGC2-citrin). Those proteins supply the aspartate synthesized... (Review)
Review
In this review we discuss the structure and functions of the aspartate/glutamate carriers (AGC1-aralar and AGC2-citrin). Those proteins supply the aspartate synthesized within mitochondrial matrix to the cytosol in exchange for glutamate and a proton. A structure of an AGC carrier is not available yet but comparative 3D models were proposed. Moreover, transport assays performed by using the recombinant AGC1 and AGC2, reconstituted into liposome vesicles, allowed to explore the kinetics of those carriers and to reveal their specific transport properties. AGCs participate to a wide range of cellular functions, as the control of mitochondrial respiration, calcium signaling and antioxydant defenses. AGC1 might also play peculiar tissue-specific functions, as it was found to participate to cell-to-cell metabolic symbiosis in the retina. On the other hand, AGC1 is involved in the glutamate-mediated excitotoxicity in neurons and AGC gene or protein alterations were discovered in rare human diseases. Accordingly, a mice model of AGC1 gene knock-out presented with growth delay and generalized tremor, with myelinisation defects. More recently, AGC was proposed to play a crucial role in tumor metabolism as observed from metabolomic studies showing that the asparate exported from the mitochondrion by AGC1 is employed in the regeneration of cytosolic glutathione. Therefore, given the central role of AGCs in cell metabolism and human pathology, drug screening are now being developed to identify pharmacological modulators of those carriers. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Topics: Amino Acid Sequence; Animals; Aspartic Acid; Biological Transport, Active; Calcium-Binding Proteins; Cattle; Consensus Sequence; Glutamic Acid; Humans; Malates; Mice; Mitochondria; Mitochondrial Membrane Transport Proteins; Models, Molecular; NAD; Neoplasm Proteins; Organ Specificity; Organic Anion Transporters; Oxidation-Reduction; Protein Conformation; Sequence Alignment; Sequence Homology, Amino Acid
PubMed: 27132995
DOI: 10.1016/j.bbamcr.2016.04.011 -
Biochemical Society Transactions Dec 2023SLC25A51 is the primary mitochondrial NAD+ transporter in humans and controls many local reactions by mediating the influx of oxidized NAD+. Intriguingly, SLC25A51 lacks... (Review)
Review
SLC25A51 is the primary mitochondrial NAD+ transporter in humans and controls many local reactions by mediating the influx of oxidized NAD+. Intriguingly, SLC25A51 lacks several key features compared with other members in the mitochondrial carrier family, thus its molecular mechanism has been unclear. A deeper understanding would shed light on the control of cellular respiration, the citric acid cycle, and free NAD+ concentrations in mammalian mitochondria. This review discusses recent insights into the transport mechanism of SLC25A51, and in the process highlights a multitiered regulation that governs NAD+ transport. The aspects regulating SLC25A51 import activity can be categorized as contributions from (1) structural characteristics of the transporter itself, (2) its microenvironment, and (3) distinctive properties of the transported ligand. These unique mechanisms further evoke compelling new ideas for modulating the activity of this transporter, as well as new mechanistic models for the mitochondrial carrier family.
Topics: Animals; Humans; Biological Transport; Cell Respiration; Mammals; Mitochondria; Mitochondrial Membrane Transport Proteins; NAD
PubMed: 38108469
DOI: 10.1042/BST20220318 -
Scientific Reports Jan 2017Aquaporins are membrane integral proteins responsible for the transmembrane transport of water and other small neutral molecules. Despite their well-acknowledged...
Aquaporins are membrane integral proteins responsible for the transmembrane transport of water and other small neutral molecules. Despite their well-acknowledged importance in water transport, their significance in gas transport processes remains unclear. Growing evidence points to the involvement of plant aquaporins in CO delivery for photosynthesis. The role of these channel proteins in the transport of O and other gases may also be more important than previously envisioned. In this study, we examined O permeability of various human, plant, and fungal aquaporins by co-expressing heterologous aquaporin and myoglobin in yeast. Two of the most promising O-transporters (Homo sapiens AQP1 and Nicotiana tabacum PIP1;3) were confirmed to facilitate O transport in the spectrophotometric assay using yeast protoplasts. The over-expression of NtPIP1;3 in yeasts significantly increased their O uptake rates in suspension culture. In N. tabacum roots subjected to hypoxic hydroponic conditions, the transcript levels of the O-transporting aquaporin NtPIP1;3 significantly increased after the seven-day hypoxia treatment, which was accompanied by the increase of ATP levels in the apical root segments. Our results suggest that the functional significance of aquaporin-mediated O transport and the possibility of controlling the rate of transmembrane O transport should be further explored.
Topics: Adenosine Triphosphate; Animals; Aquaporins; Biological Transport; Humans; Hypoxia; Myoglobin; Oxygen; Oxygen Consumption; Plant Roots; Protoplasts; RNA, Messenger; Saccharomyces cerevisiae; Sperm Whale; Nicotiana
PubMed: 28079178
DOI: 10.1038/srep40411 -
Critical Reviews in Biomedical... 1989This review focuses on the theory of oxygen transport to tissue and presents the state of the art in mathematical modeling of transport phenomena. Results obtained with... (Review)
Review
This review focuses on the theory of oxygen transport to tissue and presents the state of the art in mathematical modeling of transport phenomena. Results obtained with the classic Krogh tissue-cylinder model and recent advances in mathematical modeling of hemoglobin-oxygen kinetics, the role of hemoglobin and myoglobin in facilitating oxygen diffusion, and the role of morphologic and hemodynamic heterogeneities in oxygen transport in the microcirculation are critically discussed. Mathematical models simulate different parts of the pathway of oxygen molecules from the red blood cell, through the plasma, the endothelial cell, other elements of the vascular wall, and the extra- and intracellular space. Special attention in the review is devoted to intracapillary transport, which has been the subject of intensive theoretical research in the last decade. Models of pre- and postcapillary oxygen transport are also discussed. Applications to specific organs and tissues are reviewed, including skeletal muscle, myocardium, brain, lungs, arterial wall, and skin. Unresolved problems and major gaps in our knowledge of the mechanisms of oxygen transport are identified.
Topics: Biological Transport; Cell Membrane Permeability; Diffusion; Humans; Kinetics; Microcirculation; Models, Theoretical; Muscles; Oxygen; Oxygen Consumption; Oxyhemoglobins
PubMed: 2673661
DOI: No ID Found