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Angewandte Chemie (International Ed. in... Feb 2024Cable bacteria are multicellular, filamentous bacteria that use internal conductive fibers to transfer electrons over centimeter distances from donors within anoxic...
Cable bacteria are multicellular, filamentous bacteria that use internal conductive fibers to transfer electrons over centimeter distances from donors within anoxic sediment layers to oxygen at the surface. We extracted the fibers and used them as free-standing bio-based electrodes to investigate their electrocatalytic behavior. The fibers catalyzed the reversible interconversion of oxygen and water, and an electric current was running through the fibers even when the potential difference was generated solely by a gradient of oxygen concentration. Oxygen reduction as well as oxygen evolution were confirmed by optical measurements. Within living cable bacteria, oxygen reduction by direct electrocatalysis on the fibers and not by membrane-bound proteins readily explains exceptionally high cell-specific oxygen consumption rates observed in the oxic zone, while electrocatalytic water oxidation may provide oxygen to cells in the anoxic zone.
Topics: Electron Transport; Geologic Sediments; Sulfides; Oxidation-Reduction; Bacteria; Oxygen; Water; Electrodes
PubMed: 38018379
DOI: 10.1002/anie.202312647 -
The Journal of Physiology Dec 2023Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However,...
Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O ) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow-up MRI was performed 6-months postpartum (n = 16/20). MRI techniques included phase-contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAo ), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAo and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O delivery in the DAo , UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental-fetal O transport and consumption were similar between left and right lateral maternal positions. In comparison to non-pregnant findings, DAo and UtA O delivery and pelvic O consumption increased, while lower-limb consumption remained constant , despite reduced external iliac artery O delivery in late gestation. KEY POINTS: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood. Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus. This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O consumption (gravid uterus, fetus, placenta, lower limbs) was preserved. Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta). Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O delivery.
Topics: Female; Humans; Pregnancy; Feasibility Studies; Fetus; Magnetic Resonance Imaging; Oxygen; Oxygen Consumption; Placenta; Vena Cava, Superior
PubMed: 37906114
DOI: 10.1113/JP285097 -
Science Advances Dec 2023Oxygen deprivation and excess are both toxic. Thus, the body's ability to adapt to varying oxygen tensions is critical for survival. While the hypoxia transcriptional...
Oxygen deprivation and excess are both toxic. Thus, the body's ability to adapt to varying oxygen tensions is critical for survival. While the hypoxia transcriptional response has been well studied, the post-translational effects of oxygen have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to varying oxygen tensions. In particular, several extracellular matrix (ECM) proteins are stabilized in the lung under both hypoxia and hyperoxia. Furthermore, we show that complex 1 of the electron transport chain is destabilized in hyperoxia, in accordance with the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a hyperoxia transcriptional regulator, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of varying oxygen tensions on protein turnover rates and identifies tissue-specific mediators of oxygen-dependent responses.
Topics: Animals; Mice; Brain; Hyperoxia; Hypoxia; Lung; Oxygen
PubMed: 38064566
DOI: 10.1126/sciadv.adj4884 -
International Journal of Molecular... Jan 2024HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of... (Review)
Review
HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future.
Topics: Humans; Hyperoxia; Hyperbaric Oxygenation; Oxygen; Hypoxia; Inflammation
PubMed: 38255851
DOI: 10.3390/ijms25020777 -
Developmental Cell Apr 2024Control of protein stoichiometry is essential for cell function. Mitochondrial oxidative phosphorylation (OXPHOS) presents a complex stoichiometric challenge as the...
Control of protein stoichiometry is essential for cell function. Mitochondrial oxidative phosphorylation (OXPHOS) presents a complex stoichiometric challenge as the ratio of the electron transport chain (ETC) and ATP synthase must be tightly controlled, and assembly requires coordinated integration of proteins encoded in the nuclear and mitochondrial genome. How correct OXPHOS stoichiometry is achieved is unknown. We identify the Mitochondrial Regulatory hub for respiratory Assembly (MiRA) platform, which synchronizes ETC and ATP synthase biogenesis in yeast. Molecularly, this is achieved by a stop-and-go mechanism: the uncharacterized protein Mra1 stalls complex IV assembly. Two "Go" signals are required for assembly progression: binding of the complex IV assembly factor Rcf2 and Mra1 interaction with an Atp9-translating mitoribosome induce Mra1 degradation, allowing synchronized maturation of complex IV and the ATP synthase. Failure of the stop-and-go mechanism results in cell death. MiRA controls OXPHOS assembly, ensuring correct stoichiometry of protein machineries encoded by two different genomes.
Topics: Oxidative Phosphorylation; Saccharomyces cerevisiae; Mitochondria; Saccharomyces cerevisiae Proteins; Mitochondrial Proton-Translocating ATPases; Electron Transport Complex IV; Mitochondrial Proteins
PubMed: 38508182
DOI: 10.1016/j.devcel.2024.02.011 -
Chemosphere Oct 2023Increasingly prominent pollution levels and strong regional characteristics of O, especially in economically developed eastern China, called for a regional cooperation...
Increasingly prominent pollution levels and strong regional characteristics of O, especially in economically developed eastern China, called for a regional cooperation strategy based on transport quantification. This study adopted the complex networks to construct the O Transport Network (OTN) to explore characteristics in eastern China in the summer of 2017 and 2021, whose results were afterward verified with spatial source apportionment results simulated with WRF-CMAQ-ISAM. As OTN suggested, O transport showed stronger and faster characteristics in eastern China in 2021 than in 2017, judging from changes in the network density, number of connections, transport ranges, and transport paths. Among all cluster communities, inland Shandong was the most important O transport hub, the Central Community was the largest community, and the Southern Community showed the closest inter-city transport relationships. In- and out-weighted degrees in OTN showed relatively superior consistency with the transport matrix obtained with WRF-CMAQ-ISAM, and can be explained by wind fields. Generally, O pollution in the whole eastern China showed more frequent intra-regional transport and more strengthened inter-city correlations in 2021 than in 2017, meanwhile, northerly and southerly cities exhibited strengthening and weakening trends in O transport, respectively. Despite the completely different principles of complex networks and air quality models, their results were mutually verifiable. This study presented a comprehensive understanding of O transport in eastern China for further formulation of regional collaborative strategies and provided the methodological verification for applying complex networks in the atmospheric environment field.
Topics: Air Pollutants; Ozone; Models, Theoretical; Environmental Monitoring; Air Pollution; China
PubMed: 37336440
DOI: 10.1016/j.chemosphere.2023.139258 -
Scientific Reports Sep 2023Some of the prominent features of long-term memory formation include protein synthesis, gene expression, enhanced neurotransmitter release, increased excitability, and...
Some of the prominent features of long-term memory formation include protein synthesis, gene expression, enhanced neurotransmitter release, increased excitability, and formation of new synapses. As these processes are critically dependent on mitochondrial function, we hypothesized that increased mitochondrial respiration and dynamics would play a prominent role in memory formation. To address this possibility, we measured mitochondrial oxygen consumption (OCR) in hippocampal tissue punches from trained and untrained animals. Our results show that context fear training significantly increased basal, ATP synthesis-linked, and maximal OCR in the Shaffer collateral-CA1 synaptic region, but not in the CA1 cell body layer. These changes were recapitulated in synaptosomes isolated from the hippocampi of fear-trained animals. As dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, we examined its role in the increased mitochondrial respiration observed after fear training. Drp1 inhibitors decreased the training-associated enhancement of OCR and impaired contextual fear memory, but did not alter the number of synaptosomes containing mitochondria. Taken together, our results show context fear training increases presynaptic mitochondria respiration, and that Drp-1 mediated enhanced energy production in CA1 pre-synaptic terminals is necessary for context fear memory that does not result from an increase in the number of synaptosomes containing mitochondria or an increase in mitochondrial mass within the synaptic layer.
Topics: Animals; Biological Transport; Oxygen Consumption; Synapses; Memory Disorders; Mitochondria
PubMed: 37660191
DOI: 10.1038/s41598-023-40877-0 -
Biochimica Et Biophysica Acta.... Jun 2024Iron‑sulfur (FeS) clusters are cofactors of numerous proteins involved in essential cellular functions including respiration, protein translation, DNA synthesis and... (Review)
Review
Iron‑sulfur (FeS) clusters are cofactors of numerous proteins involved in essential cellular functions including respiration, protein translation, DNA synthesis and repair, ribosome maturation, anti-viral responses, and isopropylmalate isomerase activity. Novel FeS proteins are still being discovered due to the widespread use of cryogenic electron microscopy (cryo-EM) and elegant genetic screens targeted at protein discovery. A complex sequence of biochemical reactions mediated by a conserved machinery controls biosynthesis of FeS clusters. In eukaryotes, a remarkable epistasis has been observed: the mitochondrial machinery, termed ISC (Iron-Sulfur Cluster), lies upstream of the cytoplasmic machinery, termed CIA (Cytoplasmic Iron‑sulfur protein Assembly). The basis for this arrangement is the production of a hitherto uncharacterized intermediate, termed X-S or (Fe-S), produced in mitochondria by the ISC machinery, exported by the mitochondrial ABC transporter Atm1 (ABCB7 in humans), and then utilized by the CIA machinery for the cytoplasmic/nuclear FeS cluster assembly. Genetic and biochemical findings supporting this sequence of events are herein presented. New structural views of the Atm1 transport phases are reviewed. The key compartmental roles of glutathione in cellular FeS cluster biogenesis are highlighted. Finally, data are presented showing that every one of the ten core components of the mitochondrial ISC machinery and Atm1, when mutated or depleted, displays similar phenotypes: mitochondrial and cytoplasmic FeS clusters are both rendered deficient, consistent with the epistasis noted above.
Topics: Mitochondria; Iron-Sulfur Proteins; Humans; Cytoplasm; Saccharomyces cerevisiae Proteins; ATP-Binding Cassette Transporters; Saccharomyces cerevisiae; Mitochondrial Proteins; Glutathione
PubMed: 38641180
DOI: 10.1016/j.bbamcr.2024.119733 -
International Journal of Molecular... Sep 2023This review analyzes the causes and consequences of apoptosis resulting from oxidative stress that occurs in mitochondria and cells exposed to the toxic effects of... (Review)
Review
This review analyzes the causes and consequences of apoptosis resulting from oxidative stress that occurs in mitochondria and cells exposed to the toxic effects of different-valence heavy metals (Ag, Tl, Hg, Cd, Pb, Al, Ga, In, As, Sb, Cr, and U). The problems of the relationship between the integration of these toxic metals into molecular mechanisms with the subsequent development of pathophysiological processes and the appearance of diseases caused by the accumulation of these metals in the body are also addressed in this review. Such apoptosis is characterized by a reduction in cell viability, the activation of caspase-3 and caspase-9, the expression of pro-apoptotic genes ( and ), and the activation of protein kinases (ERK, JNK, p53, and p38) by mitogens. Moreover, the oxidative stress manifests as the mitochondrial permeability transition pore (MPTP) opening, mitochondrial swelling, an increase in the production of reactive oxygen species (ROS) and HO, lipid peroxidation, cytochrome c release, a decline in the inner mitochondrial membrane potential (ΔΨ), a decrease in ATP synthesis, and reduced glutathione and oxygen consumption as well as cytoplasm and matrix calcium overload due to Ca release from the endoplasmic reticulum (ER). The apoptosis and respiratory dysfunction induced by these metals are discussed regarding their interaction with cellular and mitochondrial thiol groups and Fe metabolism disturbance. Similarities and differences in the toxic effects of Tl from those of other heavy metals under review are discussed. Similarities may be due to the increase in the cytoplasmic calcium concentration induced by Tl and these metals. One difference discussed is the failure to decrease Tl toxicity through metallothionein-dependent mechanisms. Another difference could be the decrease in reduced glutathione in the matrix due to the reversible oxidation of Tl to Tl near the centers of ROS generation in the respiratory chain. The latter may explain why thallium toxicity to humans turned out to be higher than the toxicity of mercury, lead, cadmium, copper, and zinc.
Topics: Humans; Reactive Oxygen Species; Calcium; Hydrogen Peroxide; Mitochondrial Membrane Transport Proteins; Mitochondria; Apoptosis; Oxidative Stress; Cadmium; Glutathione; Metals, Heavy; Membrane Potential, Mitochondrial
PubMed: 37833908
DOI: 10.3390/ijms241914459 -
Cell Reports Sep 2023Copper is a critical element for eukaryotic life involved in numerous cellular functions, including redox balance, but is toxic in excess. Therefore, tight regulation of...
Copper is a critical element for eukaryotic life involved in numerous cellular functions, including redox balance, but is toxic in excess. Therefore, tight regulation of copper acquisition and homeostasis is essential for cell physiology and survival. Here, we identify a different regulatory mechanism for cellular copper homeostasis that requires the presence of an endogenous retroviral envelope glycoprotein called Refrex1. We show that cells respond to elevated extracellular copper by increasing the expression of Refrex1, which regulates copper acquisition through interaction with the main copper transporter CTR1. Downmodulation of Refrex1 results in intracellular copper accumulation leading to reactive oxygen species (ROS) production and subsequent apoptosis, which is prevented by copper chelator treatment. Our results show that Refrex1 has been co-opted for its ability to regulate copper entry through CTR1 in order to limit copper excess, redox imbalance, and ensuing cell death, strongly suggesting that other endogenous retroviruses may have similar metabolic functions among vertebrates.
Topics: Animals; Copper; Copper Transporter 1; Cell Survival; Endogenous Retroviruses; Cation Transport Proteins; Homeostasis
PubMed: 37682705
DOI: 10.1016/j.celrep.2023.113065