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The Journal of Thoracic and... Jul 2020
Topics: Lung Transplantation; Oxygenators, Membrane
PubMed: 31672391
DOI: 10.1016/j.jtcvs.2019.09.124 -
The Journal of Biological Chemistry Sep 2023Iron-sulfur clusters (ISC) are essential cofactors that participate in electron transfer, environmental sensing, and catalysis. Amongst the most ancient ISC-containing...
Iron-sulfur clusters (ISC) are essential cofactors that participate in electron transfer, environmental sensing, and catalysis. Amongst the most ancient ISC-containing proteins are the ferredoxin (FDX) family of electron carriers. Humans have two FDXs- FDX1 and FDX2, both of which are localized to mitochondria, and the latter of which is itself important for ISC synthesis. We have previously shown that hypoxia can eliminate the requirement for some components of the ISC biosynthetic pathway, but FDXs were not included in that study. Here, we report that FDX1, but not FDX2, is dispensable under 1% O in cultured human cells. We find that FDX1 is essential for production of the lipoic acid cofactor, which is synthesized by the ISC-containing enzyme lipoyl synthase. While hypoxia can rescue the growth phenotype of either FDX1 or lipoyl synthase KO cells, lipoylation in these same cells is not rescued, arguing against an alternative biosynthetic route or salvage pathway for lipoate in hypoxia. Our work reveals the divergent roles of FDX1 and FDX2 in mitochondria, identifies a role for FDX1 in lipoate synthesis, and suggests that loss of lipoic acid can be tolerated under low oxygen tensions in cell culture.
Topics: Humans; Ferredoxins; Lipoylation; Thioctic Acid; Cell Hypoxia; Gene Knockout Techniques; Oxygen; Proteome; Sulfurtransferases; Binding Sites; Protein Stability; Protein Biosynthesis
PubMed: 37481209
DOI: 10.1016/j.jbc.2023.105075 -
Free Radical Biology & Medicine Aug 2019Cyanobacteria played an important role in the evolution of Early Earth and the biosphere. They are responsible for the oxygenation of the atmosphere and oceans since the... (Review)
Review
Cyanobacteria played an important role in the evolution of Early Earth and the biosphere. They are responsible for the oxygenation of the atmosphere and oceans since the Great Oxidation Event around 2.4 Ga, debatably earlier. They are also major primary producers in past and present oceans, and the ancestors of the chloroplast. Nevertheless, the identification of cyanobacteria in the early fossil record remains ambiguous because the morphological criteria commonly used are not always reliable for microfossil interpretation. Recently, new biosignatures specific to cyanobacteria were proposed. Here, we review the classic and new cyanobacterial biosignatures. We also assess the reliability of the previously described cyanobacteria fossil record and the challenges of molecular approaches on modern cyanobacteria. Finally, we suggest possible new calibration points for molecular clocks, and strategies to improve our understanding of the timing and pattern of the evolution of cyanobacteria and oxygenic photosynthesis.
Topics: Biological Evolution; Chloroplasts; Cyanobacteria; Fossils; Oxidation-Reduction; Oxygen; Photosynthesis
PubMed: 31078731
DOI: 10.1016/j.freeradbiomed.2019.05.007 -
Nature Communications Jul 2023Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved...
Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.
Topics: Animals; Swine; Lysine; Cytochromes c; Phosphorylation; Acetylation; Protein Processing, Post-Translational; Apoptosis; Cell Respiration; Reperfusion Injury; Muscle, Skeletal
PubMed: 37443314
DOI: 10.1038/s41467-023-39820-8 -
Clinical and Applied... 2021Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on... (Review)
Review
Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.
Topics: Animals; Blood Platelets; Cardiopulmonary Bypass; Cell-Derived Microparticles; Extracorporeal Membrane Oxygenation; Heart-Assist Devices; Hemolysis; Hemostatic Disorders; Humans; Oxygenators, Membrane; Platelet Activation; Prosthesis Design; Prosthesis Implantation; Risk Assessment; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 33571008
DOI: 10.1177/1076029620982374 -
Cellular and Molecular Life Sciences :... Jul 2023The precise characterization of oxygen-sensing pathways and the identification of pO-regulated gene expression are both issues of critical importance. The O-sensing... (Review)
Review
The precise characterization of oxygen-sensing pathways and the identification of pO-regulated gene expression are both issues of critical importance. The O-sensing system plays crucial roles in almost all the pivotal human processes, including the stem cell specification, the growth and development of tissues (such as embryogenesis), the modulation of intermediate metabolism (including the shift of the glucose metabolism from oxidative to anaerobic ATP production and vice versa), and the control of blood pressure. The solid cancer microenvironment is characterized by low oxygen levels and by the consequent activation of the hypoxia response that, in turn, allows a complex adaptive response characterized mainly by neoangiogenesis and metabolic reprogramming. Recently, incredible advances in molecular genetic methodologies allowed the genome editing with high efficiency and, above all, the precise identification of target cells/tissues. These new possibilities and the knowledge of the mechanisms of adaptation to hypoxia suggest the effective development of new therapeutic approaches based on the manipulation, targeting, and exploitation of the oxygen-sensor system molecular mechanisms.
Topics: Humans; Gene Editing; Hypoxia; Oxygen; Cell Hypoxia; Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Von Hippel-Lindau Tumor Suppressor Protein; Tumor Microenvironment
PubMed: 37477829
DOI: 10.1007/s00018-023-04852-2 -
Biochemical Society Transactions Jun 2020Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications.... (Review)
Review
Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications. Co-ordinated mechanisms have evolved for sensing and responding to hypoxia, which involve diverse biological outputs, with the main aim of restoring oxygen homeostasis. This includes a dynamic gene transcriptional response, the central drivers of which are the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are regulated in an oxygen-dependent manner and while their role in hypoxia is well established, it is apparent that other key players are required for gene expression control in hypoxia. In this review, we highlight the current understanding of the known and potential molecular mechanisms underpinning gene transcriptional responses to hypoxia in mammals, with a focus on oxygen-dependent effects on chromatin structure.
Topics: Animals; Cell Hypoxia; Chromatin; Gene Expression Profiling; Gene Expression Regulation; Homeostasis; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Methylation; Oxygen; Protein Processing, Post-Translational; RNA, Untranslated; Transcription Factors; Transcription, Genetic
PubMed: 32369557
DOI: 10.1042/BST20191106 -
PloS One 2022Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and...
Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2 transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2 transfer was less affected.
Topics: Adult; Blood Volume; Carbon Dioxide; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Oxygen; Oxygenators; Regional Blood Flow
PubMed: 35108345
DOI: 10.1371/journal.pone.0263360 -
The New Phytologist Feb 2020Oxygenic phototrophs have played a fundamental role in Earth's history by enabling the rise of atmospheric oxygen (O ) and paving the way for animal evolution.... (Review)
Review
Oxygenic phototrophs have played a fundamental role in Earth's history by enabling the rise of atmospheric oxygen (O ) and paving the way for animal evolution. Understanding the origins of oxygenic photosynthesis and Cyanobacteria is key when piecing together the events around Earth's oxygenation. It is likely that photosynthesis evolved within bacterial lineages that are not extant, so it can be challenging when studying the early history of photosynthesis. Recent genomic and molecular evolution studies have transformed our understanding about the evolution of photosynthetic reaction centres and the evolution of Cyanobacteria. The evidence reviewed here highlights some of the most recent advances on the origin of photosynthesis both at the genomic and gene family levels.
Topics: Biological Evolution; Cyanobacteria; Oxygen; Photosynthesis; Photosynthetic Reaction Center Complex Proteins; Protein Conformation
PubMed: 31598981
DOI: 10.1111/nph.16249 -
Experimental & Molecular Medicine Mar 2024Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response... (Review)
Review
Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, orchestrate the cellular hypoxic response, activating genes to increase the oxygen supply and reduce expenditure. Under conditions of excess oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell survival. Hypoxia and oxidative stress are core hallmarks of solid tumors and activated HIFs and NRF2 play pivotal roles in tumor growth and progression. The complex interplay between hypoxia and oxidative stress within the tumor microenvironment adds another layer of intricacy to the HIF and NRF2 signaling systems. This review aimed to elucidate the dynamic changes and functions of the HIF and NRF2 signaling pathways in response to conditions of hypoxia and oxidative stress, emphasizing their implications within the tumor milieu. Additionally, this review explored the elaborate interplay between HIFs and NRF2, providing insights into the significance of these interactions for the development of novel cancer treatment strategies.
Topics: Humans; Cell Hypoxia; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; NF-E2-Related Factor 2; Oxidative Stress; Oxygen; Tumor Microenvironment
PubMed: 38424190
DOI: 10.1038/s12276-024-01180-8