Cellular oxygen sensing by mitochondria: old questions, new insight

2000 ◽  
Vol 88 (5) ◽  
pp. 1880-1889 ◽  
Author(s):  
Navdeep S. Chandel ◽  
Paul T. Schumacker
Keyword(s):  
Second Messengers ◽  
Cell Types ◽  
Tissue Level ◽  
Cellular Level ◽  
Signaling Cascades ◽  
Adaptive Responses ◽  
Signaling Systems ◽  
Multiple Sensors ◽  
Cell Death Pathways ◽  
Cellular Oxygen

Hypoxia elicits a variety of adaptive responses at the tissue level, at the cellular level, and at the molecular level. A physiological response to hypoxia requires the existence of an O2sensor coupled to a signal transduction system, which in turn activates the functional response. Although much has been learned about the signaling systems activated by hypoxia, no consensus exists regarding the nature of the underlying O2sensor or whether multiple sensors exist. Among previously considered mechanisms, heme proteins have been suggested to undergo allosteric modification in response to O2binding or release at different [Formula: see text] levels. Other studies suggest that ion channels may change conductance as a function of[Formula: see text], allowing them to signal the onset of hypoxia. Still other studies suggest that NADPH oxidase may decrease its generation of reactive O2species (ROS) during hypoxia. Recent data suggest that mitochondria may function as O2sensors by increasing their generation of ROS during hypoxia. These oxidant signals appear to act as second messengers in the adaptive responses to hypoxia in a variety of cell types. Such observations contribute to a growing awareness that mitochondria do more than just generate ATP, in that they initiate signaling cascades involved in adaptive responses to hypoxia and that they participate in the control of cell death pathways.

scholarly journals A 2020 view of tension-based cortical morphogenesis

2020 ◽  
Vol 117 (52) ◽  
pp. 32868-32879
Author(s):  
David C. Van Essen
Keyword(s):  
Cell Types ◽  
Tissue Level ◽  
Cellular Level ◽  
General Hypothesis ◽  
Cortical Gray Matter ◽  
Level I ◽  
Key Aspects ◽  
Des Model

Mechanical tension along the length of axons, dendrites, and glial processes has been proposed as a major contributor to morphogenesis throughout the nervous system [D. C. Van Essen, Nature 385, 313–318 (1997)]. Tension-based morphogenesis (TBM) is a conceptually simple and general hypothesis based on physical forces that help shape all living things. Moreover, if each axon and dendrite strive to shorten while preserving connectivity, aggregate wiring length would remain low. TBM can explain key aspects of how the cerebral and cerebellar cortices remain thin, expand in surface area, and acquire their distinctive folds. This article reviews progress since 1997 relevant to TBM and other candidate morphogenetic mechanisms. At a cellular level, studies of diverse cell types in vitro and in vivo demonstrate that tension plays a major role in many developmental events. At a tissue level, I propose a differential expansion sandwich plus (DES+) revision to the original TBM model for cerebral cortical expansion and folding. It invokes tangential tension and “sulcal zipping” forces along the outer cortical margin as well as tension in the white matter core, together competing against radially biased tension in the cortical gray matter. Evidence for and against the DES+ model is discussed, and experiments are proposed to address key tenets of the DES+ model. For cerebellar cortex, a cerebellar multilayer sandwich (CMS) model is proposed that can account for many distinctive features, including its unique, accordion-like folding in the adult, and experiments are proposed to address its specific tenets.

scholarly journals Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

2020 ◽  
Vol 7 (6) ◽  
pp. 200265 ◽  
Author(s):  
Charalampos Sigalas ◽  
Maegan Cremer ◽  
Annika Winbo ◽  
Samuel J. Bose ◽  
Jesse L. Ashton ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Optical Imaging ◽  
Imaging Techniques ◽  
Cell Types ◽  
Tissue Level ◽  
Cellular Level ◽  
Optical Recording ◽  
Polymorphic Ventricular Tachycardia ◽  
Cardiac Diseases

Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.

scholarly journals Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshifumi Asakura ◽  
Yohei Kondo ◽  
Kazuhiro Aoki ◽  
Honda Naoki
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Continuum Model ◽  
Tissue Level ◽  
Chemical Signals ◽  
Cellular Level ◽  
Mathematical Framework ◽  
Collective Cell Migration ◽  
The Continuum ◽  
Cell Cell

AbstractCollective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.

scholarly journals Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

2020 ◽  
Vol 22 (1) ◽  
pp. 261
Author(s):  
Abdelnaby Khalyfa ◽  
Wesley Warren ◽  
Jorge Andrade ◽  
Christopher A. Bottoms ◽  
Edward S. Rice ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cell Types ◽  
Cellular Level ◽  
Cellular Heterogeneity ◽  
Transcriptional Networks ◽  
Metabolic Dysfunction ◽  
Rna Seq ◽  
Obstructive Sleep ◽  
Differential Expressed Gene ◽  
Key Aspects

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.

scholarly journals Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors

PLoS Genetics ◽  
2013 ◽  
Vol 9 (6) ◽  
pp. e1003555 ◽  
Author(s):  
Kyoung-in Cho ◽  
MdEmdadul Haque ◽  
Jessica Wang ◽  
Minzhong Yu ◽  
Ying Hao ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Cell Types ◽  
Cone Photoreceptors ◽  
Cell Death Pathways

scholarly journals Intercellular calcium signalling between chondrocytes and synovial cells in co-culture

1998 ◽  
Vol 329 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Paola D'ANDREA ◽  
Alessandra CALABRESE ◽  
Micaela GRANDOLFO
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Structural Changes ◽  
Articular Chondrocytes ◽  
Cell Metabolism ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Cell Types ◽  
Synovial Cells ◽  
Cell Coupling

Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18α-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.

scholarly journals MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo

2018 ◽  
Vol 116 (1) ◽  
pp. 303-312 ◽  
Author(s):  
Erol C. Bayraktar ◽  
Lou Baudrier ◽  
Ceren Özerdem ◽  
Caroline A. Lewis ◽  
Sze Ham Chan ◽  
...  
Keyword(s):  
Metabolite Profiling ◽  
Cultured Cells ◽  
Transgenic Animals ◽  
Cell Types ◽  
Tissue Level ◽  
Specific Cell ◽  
Mammalian Tissues ◽  
Cell Type Specific ◽  
Untargeted Metabolite Profiling

Mitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell types within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially localized 3XHA epitope tag (MITO-Tag) for the fast isolation of mitochondria from cultured cells to generate MITO-Tag Mice. Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology, and our strategy should be generally applicable for studying other mammalian organelles in specific cell types in vivo.

scholarly journals MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo

2018 ◽  
Author(s):  
Erol Can Bayraktar ◽  
Lou Baudrier ◽  
Ceren Özerdem ◽  
Caroline A. Lewis ◽  
Sze Ham Chan ◽  
...  
Keyword(s):  
Metabolite Profiling ◽  
Cultured Cells ◽  
Transgenic Animals ◽  
Cell Types ◽  
Tissue Level ◽  
Specific Cell ◽  
Mammalian Tissues ◽  
Cell Type Specific ◽  
Untargeted Metabolite Profiling

ABSTRACTMitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell-types within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially-localized 3XHA epitope-tag (“MITO-Tag”) for the fast isolation of mitochondria from cultured cells to now generate “MITO-Tag Mice.” Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology and our strategy should be generally applicable for studying other mammalian organelles in specific cell-types in vivo.

scholarly journals Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

2021 ◽  
Author(s):  
Rammohan Shukla ◽  
Nicholas D Henkel ◽  
Marissa A Smail ◽  
Xiaojun Wu ◽  
Heather A Enright ◽  
...  
Keyword(s):  
Machine Learning ◽  
Bayesian Inference ◽  
Pyramidal Neurons ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Cellular Level ◽  
Hippocampal Subfields ◽  
Synaptic Changes ◽  
Discovery Method

We probed a transcriptomic dataset of pilocarpine-induced TLE using various ontological, machine-learning, and systems-biology approaches. We showed that, underneath the complex and penetrant changes, moderate-to-subtle upregulated homeostatic and downregulated synaptic changes associated with the dentate gyrus and hippocampal subfields could not only predict TLE but various other forms of epilepsy. At the cellular level, pyramidal neurons and interneurons showed disparate changes, whereas the proportion of non-neuronal cells increased steadily. A probabilistic Bayesian network demonstrated an aberrant and oscillating physiological interaction between oligodendrocytes and interneurons in driving seizures. Validating the Bayesian inference, we showed that the cell types driving the seizures were associated with known antiepileptic and epileptic drugs. These findings provide predictive biomarkers of epilepsy, insights into the cellular connections and causal changes associated with TLE, and a drug discovery method focusing on these events.

scholarly journals Water contaminated with Didymosphenia geminata alters fish cell line viability

2018 ◽  
Author(s):  
Pamela Olivares ◽  
Matias Peredo-Parada ◽  
Viviana Chavez ◽  
Erico Carmona ◽  
Allison Astuya ◽  
...  
Keyword(s):  
River System ◽  
Cell Types ◽  
Complex Problem ◽  
Cellular Level ◽  
Lower Sensitivity ◽  
Fish Cell ◽  
Fish Cell Lines ◽  
Didymosphenia Geminata ◽  
Chronic Effects ◽  
The Moment

Didymosphenia geminata (D. geminata) in Chilean rivers is a complex problem. Its biology and effects on ecosystems is still being studied, at the moment not research has focused on its D. geminata effects at the cellular level. We developed an artificial river system to maintain D. geminata study material and evaluate effects of water contaminated with this diatom on the viability of two fish cell lines. Results indicate that CHSE-214 cells are sensitive to increasing D. geminata extract concentrations, reducing crop viability by 50% when exposed for 24 hours at a 0.01V/V dilution and reducing proliferative capacity by 70% on a 5 day temporal curve. SHK-1 cells showed lower sensitivity, presenting a decrease of 20% in viability at 24 hours, and a lower cell proliferation rate by day 5, but higher than of the CHSE-214 cells. Both lines were affected by exposure to D. geminata extracts, but CHSE-214 lines were more sensitive to polyphenols extracted from the microalgae. We conclude that certain cell types are sensitive to D. geminata in rivers, meaning that chronic effects on aquatic species contaminated with this diatom should be observed. Effects of this plague at a cellular level can be further studied to understand its full impact on river ecosystems.

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