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Nature Mar 2021Mitochondria are specialized eukaryotic organelles that have a dedicated function in oxygen respiration and energy production. They evolved about 2 billion years ago...
Mitochondria are specialized eukaryotic organelles that have a dedicated function in oxygen respiration and energy production. They evolved about 2 billion years ago from a free-living bacterial ancestor (probably an alphaproteobacterium), in a process known as endosymbiosis. Many unicellular eukaryotes have since adapted to life in anoxic habitats and their mitochondria have undergone further reductive evolution. As a result, obligate anaerobic eukaryotes with mitochondrial remnants derive their energy mostly from fermentation. Here we describe 'Candidatus Azoamicus ciliaticola', which is an obligate endosymbiont of an anaerobic ciliate and has a dedicated role in respiration and providing energy for its eukaryotic host. 'Candidatus A. ciliaticola' contains a highly reduced 0.29-Mb genome that encodes core genes for central information processing, the electron transport chain, a truncated tricarboxylic acid cycle, ATP generation and iron-sulfur cluster biosynthesis. The genome encodes a respiratory denitrification pathway instead of aerobic terminal oxidases, which enables its host to breathe nitrate instead of oxygen. 'Candidatus A. ciliaticola' and its ciliate host represent an example of a symbiosis that is based on the transfer of energy in the form of ATP, rather than nutrition. This discovery raises the possibility that eukaryotes with mitochondrial remnants may secondarily acquire energy-providing endosymbionts to complement or replace functions of their mitochondria.
Topics: Adenosine Triphosphate; Anaerobiosis; Bacteria; Biological Evolution; Cell Respiration; Ciliophora; Citric Acid Cycle; Denitrification; Electron Transport; Energy Metabolism; Genome, Bacterial; Host Microbial Interactions; Mitochondria; Nitrates; Oxygen; Phylogeny; Symbiosis
PubMed: 33658719
DOI: 10.1038/s41586-021-03297-6 -
Journal of Chemical Theory and... Jul 2018The balance of normal and radial (lateral) diffusion of oxygen in phospholipid membranes is critical for biological function. Based on the Smoluchowski equation for the...
The balance of normal and radial (lateral) diffusion of oxygen in phospholipid membranes is critical for biological function. Based on the Smoluchowski equation for the inhomogeneous solubility-diffusion model, Bayesian analysis (BA) can be applied to molecular dynamics trajectories of oxygen to extract the free energy and the normal and radial diffusion profiles. This paper derives a theoretical formalism to convert these profiles into characteristic times and lengths associated with entering, escaping, or completely crossing the membrane. The formalism computes mean first passage times and holds for any process described by rate equations between discrete states. BA of simulations of eight model membranes with varying lipid composition and temperature indicate that oxygen travels 3 to 5 times further in the radial than in the normal direction when crossing the membrane in a time of 15 to 32 ns, thereby confirming the anisotropy of passive oxygen transport in membranes. Moreover, the preceding times and distances estimated from the BA are compared to the aggregate of 280 membrane exits explicitly observed in the trajectories. BA predictions for the distances of oxygen radial diffusion within the membrane are statistically indistinguishable from the corresponding simulation values, yet BA oxygen exit times from the membrane interior are approximately 20% shorter than the simulation values, averaged over seven systems. The comparison supports the BA approach and, therefore, the applicability of the Smoluchowski equation to membrane diffusion. Given the shorter trajectories required for the BA, these results validate the BA as a computationally attractive alternative to direct observation of exits when estimating characteristic times and radial distances. The effect of collective membrane undulations on the BA is also discussed.
Topics: Bayes Theorem; Cell Membrane Permeability; Diffusion; Lipid Bilayers; Molecular Dynamics Simulation; Oxygen; Permeability; Solubility; Thermodynamics
PubMed: 29894626
DOI: 10.1021/acs.jctc.8b00115 -
Plant, Cell & Environment Jun 2017How water moves through leaves, and where the phase change from liquid to vapour occurs within leaves, remain largely mysterious. Some time ago, we suggested that the... (Review)
Review
How water moves through leaves, and where the phase change from liquid to vapour occurs within leaves, remain largely mysterious. Some time ago, we suggested that the stable isotope composition of leaf water may contain information on transport pathways beyond the xylem, through differences in the development of gradients in enrichment within the various pathways. Subsequent testing of this suggestion provided ambiguous results and even questioned the existence of gradients in enrichment within the mesophyll. In this review, we bring together recent theoretical developments in understanding leaf water transport pathways and stable isotope theory to map a path for future work into understanding pathways of water transport and leaf water stable isotope composition. We emphasize the need for a spatially, anatomically and isotopically explicit model of leaf water transport.
Topics: Biological Transport; Deuterium; Models, Biological; Oxygen Isotopes; Plant Leaves; Water; Xylem
PubMed: 27739589
DOI: 10.1111/pce.12845 -
Genome Apr 2018Hydrogen sulfide (HS) is a natural toxicant in some aquatic environments that has diverse molecular targets. It binds to oxygen transport proteins, rendering them...
Hydrogen sulfide (HS) is a natural toxicant in some aquatic environments that has diverse molecular targets. It binds to oxygen transport proteins, rendering them non-functional by reducing oxygen-binding affinity. Hence, organisms permanently inhabiting HS-rich environments are predicted to exhibit adaptive modifications to compensate for the reduced capacity to transport oxygen. We investigated 10 lineages of fish of the family Poeciliidae that have colonized freshwater springs rich in HS-along with related lineages from non-sulfidic environments-to test hypotheses about the expression and evolution of oxygen transport genes in a phylogenetic context. We predicted shifts in the expression of and signatures of positive selection on oxygen transport genes upon colonization of HS-rich habitats. Our analyses indicated significant shifts in gene expression for multiple hemoglobin genes in lineages that have colonized HS-rich environments, and three hemoglobin genes exhibited relaxed selection in sulfidic compared to non-sulfidic lineages. However, neither changes in gene expression nor signatures of selection were consistent among all lineages in HS-rich environments. Oxygen transport genes may consequently be predictable targets of selection during adaptation to sulfidic environments, but changes in gene expression and molecular evolution of oxygen transport genes in HS-rich environments are not necessarily repeatable across replicated lineages.
Topics: Adaptation, Physiological; Animals; Cyprinodontiformes; Dominican Republic; Ecosystem; Evolution, Molecular; Fish Proteins; Florida; Fresh Water; Gene Expression Profiling; Geography; Hydrogen Sulfide; Membrane Transport Proteins; Mexico; Oxygen; Phylogeny
PubMed: 29227751
DOI: 10.1139/gen-2017-0051 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2019Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and... (Review)
Review
Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and transporters. Studies have shown that hypoxia increases the release of a series of inflammatory cytokines which can modulate drug metabolism. Besides, both hypoxia inducible factor 1α (HIF-1α) and microRNA-mediated pathways play a role in regulating drug metabolism. This article reviewed the impact and single-factor modulating mechanisms of drug metabolism under hypoxia, and put forward the speculation and prospects of multi-factor modulating mechanisms.
Topics: Cell Hypoxia; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Membrane Transport Proteins; MicroRNAs; Pharmaceutical Preparations
PubMed: 31008494
DOI: No ID Found -
Oxidative Medicine and Cellular... 2021Photobiomodulation with 808 nm laser light electively stimulates Complexes III and IV of the mitochondrial respiratory chain, while Complexes I and II are not...
Photobiomodulation with 808 nm laser light electively stimulates Complexes III and IV of the mitochondrial respiratory chain, while Complexes I and II are not affected. At the wavelength of 1064 nm, Complexes I, III, and IV are excited, while Complex II and some mitochondrial matrix enzymes seem to be not receptive to photons at that wavelength. Complex IV was also activated by 633 nm. The mechanism of action of wavelengths in the range 900-1000 nm on mitochondria is less understood or not described. Oxidative stress from reactive oxygen species (ROS) generated by mitochondrial activity is an inescapable consequence of aerobic metabolism. The antioxidant enzyme system for ROS scavenging can keep them under control. However, alterations in mitochondrial activity can cause an increment of ROS production. ROS and ATP can play a role in cell death, cell proliferation, and cell cycle arrest. In our work, bovine liver isolated mitochondria were irradiated for 60 sec, in continuous wave mode with 980 nm and powers from 0.1 to 1.4 W (0.1 W increment at every step) to generate energies from 6 to 84 J, fluences from 7.7 to 107.7 J/cm, power densities from 0.13 to 1.79 W/cm, and spot size 0.78 cm. The control was equal to 0 W. The activity of the mitochondria's complexes, Krebs cycle enzymes, ATP production, oxygen consumption, generation of ROS, and oxidative stress were detected. Lower powers (0.1-0.2 W) showed an inhibitory effect; those that were intermediate (0.3-0.7 W) did not display an effect, and the higher powers (0.8-1.1 W) induced an increment of ATP synthesis. Increasing the power (1.2-1.4 W) recovered the ATP production to the control level. The interaction occurred on Complexes III and IV, as well as ATP production and oxygen consumption. Results showed that 0.1 W uncoupled the respiratory chain and induced higher oxidative stress and drastic inhibition of ATP production. Conversely, 0.8 W kept mitochondria coupled and induced an increase of ATP production by increments of Complex III and IV activities. An augmentation of oxidative stress was also observed, probably as a consequence of the increased oxygen consumption and mitochondrial isolation experimental conditions. No effect was observed using 0.5 W, and no effect was observed on the enzymes of the Krebs cycle.
Topics: Animals; Cattle; Cell Respiration; Electron Transport Complex III; Electron Transport Complex IV; Female; Isocitrate Dehydrogenase; Lasers, Semiconductor; Lipid Peroxidation; Low-Level Light Therapy; Malate Dehydrogenase; Male; Mitochondria; Oxidative Phosphorylation; Oxidative Stress; Proton-Translocating ATPases; Reactive Oxygen Species; Superoxides; Temperature
PubMed: 33763170
DOI: 10.1155/2021/6626286 -
Biochimica Et Biophysica Acta Oct 2014Calcium homeostasis is central to all cellular functions and has been studied for decades. Calcium acts as a critical second messenger for both extracellular and... (Review)
Review
Calcium homeostasis is central to all cellular functions and has been studied for decades. Calcium acts as a critical second messenger for both extracellular and intracellular signaling and is fundamental in cell life and death decisions (Berridge et al., 2000) [1]. The calcium gradient in the cell is coupled with an inherent ability of the divalent cation to reversibly bind multiple target biological molecules to generate an extremely versatile signaling system [2]. Calcium signals are used by the cell to control diverse processes such as development, neurotransmitter release, muscle contraction, metabolism, autophagy and cell death. "Cellular calcium overload" is detrimental to cellular health, resulting in massive activation of proteases and phospholipases leading to cell death (Pinton et al., 2008) [3]. Historically, cell death associated with calcium ion perturbations has been primarily recognized as necrosis. Recent evidence clearly associates changes in calcium ion concentrations with more sophisticated forms of cellular demise, including apoptosis (Kruman et al., 1998; Tombal et al., 1999; Lynch et al., 2000; Orrenius et al., 2003) [4-7]. Although the endoplasmic reticulum (ER) serves as the primary calcium store in the metazoan cell, dynamic calcium release to the cytosol, mitochondria, nuclei and other organelles orchestrate diverse coordinated responses. Most evidence supports that calcium transport from the ER to mitochondria plays a significant role in regulating cellular bioenergetics, production of reactive oxygen species, induction of autophagy and apoptosis. Recently, molecular identities that mediate calcium traffic between the ER and mitochondria have been discovered (Mallilankaraman et al., 2012a; Mallilankaraman et al., 2012b; Sancak et al., 2013)[8-10]. The next questions are how they are regulated for exquisite tight control of ER-mitochondrial calcium dynamics. This review attempts to summarize recent advances in the role of calcium in regulation of ER and mitochondrial function. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.
Topics: Animals; Calcium; Calcium Signaling; Cell Death; Endoplasmic Reticulum; Energy Metabolism; Gene Expression; Humans; Mitochondria; Mitochondrial Membrane Transport Proteins; Protein Transport
PubMed: 24690484
DOI: 10.1016/j.bbamcr.2014.03.022 -
Biochimica Et Biophysica Acta Aug 2016Glutamate elicits Ca(2+) signals and workloads that regulate neuronal fate both in physiological and pathological circumstances. Oxidative phosphorylation is required in... (Review)
Review
Glutamate elicits Ca(2+) signals and workloads that regulate neuronal fate both in physiological and pathological circumstances. Oxidative phosphorylation is required in order to respond to the metabolic challenge caused by glutamate. In response to physiological glutamate signals, cytosolic Ca(2+) activates respiration by stimulation of the NADH malate-aspartate shuttle through Ca(2+)-binding to the mitochondrial aspartate/glutamate carrier (Aralar/AGC1/Slc25a12), and by stimulation of adenine nucleotide uptake through Ca(2+) binding to the mitochondrial ATP-Mg/Pi carrier (SCaMC-3/Slc25a23). In addition, after Ca(2+) entry into the matrix through the mitochondrial Ca(2+) uniporter (MCU), it activates mitochondrial dehydrogenases. In response to pathological glutamate stimulation during excitotoxicity, Ca(2+) overload, reactive oxygen species (ROS), mitochondrial dysfunction and delayed Ca(2+) deregulation (DCD) lead to neuronal death. Glutamate-induced respiratory stimulation is rapidly inactivated through a mechanism involving Poly (ADP-ribose) Polymerase-1 (PARP-1) activation, consumption of cytosolic NAD(+), a decrease in matrix ATP and restricted substrate supply. Glutamate-induced Ca(2+)-activation of SCaMC-3 imports adenine nucleotides into mitochondria, counteracting the depletion of matrix ATP and the impaired respiration, while Aralar-dependent lactate metabolism prevents substrate exhaustion. A second mechanism induced by excitotoxic glutamate is permeability transition pore (PTP) opening, which critically depends on ROS production and matrix Ca(2+) entry through the MCU. By increasing matrix content of adenine nucleotides, SCaMC-3 activity protects against glutamate-induced PTP opening and lowers matrix free Ca(2+), resulting in protracted appearance of DCD and protection against excitotoxicity in vitro and in vivo, while the lack of lactate protection during in vivo excitotoxicity explains increased vulnerability to kainite-induced toxicity in Aralar +/- mice. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
Topics: Adenosine Triphosphate; Animals; Antiporters; Calcium; Calcium Channels; Cell Respiration; Gene Expression; Glutamic Acid; Mice; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitochondrial Proteins; Neurons; Oxidative Phosphorylation; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Primary Cell Culture; Reactive Oxygen Species; Signal Transduction
PubMed: 27060251
DOI: 10.1016/j.bbabio.2016.04.003 -
Journal of the Royal Society, Interface Dec 2017Calcium (Ca) transport by mitochondria is an important component of the cell Ca homeostasis machinery in metazoans. Ca uptake by mitochondria is a major determinant of... (Review)
Review
Calcium (Ca) transport by mitochondria is an important component of the cell Ca homeostasis machinery in metazoans. Ca uptake by mitochondria is a major determinant of bioenergetics and cell fate. Mitochondrial Ca uptake occurs via the mitochondrial Ca uniporter (MCU) complex, an inner mitochondrial membrane protein assembly consisting of the MCU Ca channel, as its core component, and the MCU complex regulatory/auxiliary proteins. In this review, we summarize the current knowledge on the molecular nature of the MCU complex and its regulation by intra- and extramitochondrial levels of divalent ions and reactive oxygen species (ROS). Intracellular Ca concentration ([Ca]), mitochondrial Ca concentration ([Ca]) and mitochondrial ROS (mROS) are intricately coupled in regulating MCU activity. Here, we highlight the contribution of MCU activity to vascular endothelial cell (EC) function. Besides the ionic and oxidant regulation, ECs are continuously exposed to haemodynamic forces (either pulsatile or oscillatory fluid mechanical shear stresses, depending on the precise EC location within the arteries). Thus, we also propose an EC mechanotransduction-mediated regulation of MCU activity in the context of vascular physiology and atherosclerotic vascular disease.
Topics: Animals; Calcium Signaling; Calcium-Binding Proteins; Cation Transport Proteins; Endothelium; Homeostasis; Humans; Mechanotransduction, Cellular; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Membrane Transport Proteins; Models, Biological; Oxidation-Reduction
PubMed: 29237825
DOI: 10.1098/rsif.2017.0672 -
Biochemical Pharmacology Sep 2022Spatial and temporal control of calcium (Ca) levels is essential for the background rhythms and responses of living cells to environmental stimuli. Whatever other... (Review)
Review
Spatial and temporal control of calcium (Ca) levels is essential for the background rhythms and responses of living cells to environmental stimuli. Whatever other regulators a given cellular activity may have, localized and wider scale Ca events (sparks, transients, and waves) are hierarchical determinants of fundamental processes such as cell contraction, excitability, growth, metabolism and survival. Different cell types express specific channels, pumps and exchangers to efficiently generate and adapt Ca patterns to cell requirements. The Na/Ca exchangers (NCXs) in particular contribute to Ca homeostasis by buffering intracellular Ca loads according to the electrochemical gradients of substrate ions - i.e., Ca and sodium (Na) - and under a dynamic control of redundant regulatory processes. An interesting feature of NCX emerges from the strict relationship that connects transporter activity with cell metabolism: on the one hand NCX operates under constant control of ATP-dependent regulatory processes, on the other hand the ion fluxes generated through NCX provide mechanistic support for the Na-driven uptake of glutamate and Ca influx to fuel mitochondrial respiration. Proof of concept evidence highlights therapeutic potential of preserving a timed and balanced NCX activity in a growing rate of diseases (including excitability, neurodegenerative, and proliferative disorders) because of an improved ability of stressed cells to safely maintain ion gradients and mitochondrial bioenergetics. Here, we will summarize and review recent works that have focused on the pathophysiological roles of NCXs in balancing the two-way relationship between Ca signals and metabolism.
Topics: Biological Transport; Calcium; Homeostasis; Sodium; Sodium-Calcium Exchanger
PubMed: 35803319
DOI: 10.1016/j.bcp.2022.115163