Ancient Atmospheres and the Evolution of Oxygen Sensing Via the Hypoxia-Inducible Factor in Metazoans

Physiology ◽  
2010 ◽  
Vol 25 (5) ◽  
pp. 272-279 ◽  
Author(s):  
Cormac T. Taylor ◽  
Jennifer C. McElwain
Keyword(s):  
Oxygen Sensing ◽  
Atmospheric Oxygen ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Oxygen Levels ◽  
Selection Force ◽  
Cellular Oxygen ◽  
Hif Pathway ◽  
Evolution Of Oxygen ◽  
Oxygen Concentrations

Metazoan diversification occurred during a time when atmospheric oxygen levels fluctuated between 15 and 30%. The hypoxia-inducible factor (HIF) is a primary regulator of the adaptive transcriptional response to hypoxia. Although the HIF pathway is highly conserved, its complexity increased during periods when atmospheric oxygen concentrations were increasing. Thus atmospheric oxygen levels may have provided a selection force on the development of cellular oxygen-sensing pathways.

scholarly journals The last common ancestor of animals lacked the HIF pathway and respired in low-oxygen environments

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Daniel B Mills ◽  
Warren R Francis ◽  
Sergio Vargas ◽  
Morten Larsen ◽  
Coen PH Elemans ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Hypoxia Inducible Factor ◽  
Last Common Ancestor ◽  
Low Oxygen ◽  
Oxygen Homeostasis ◽  
Animal Phyla ◽  
Cellular Oxygen ◽  
Hif Pathway ◽  
Anaerobic Production ◽  
Oxygen Concentrations

Animals have a carefully orchestrated relationship with oxygen. When exposed to low environmental oxygen concentrations, and during periods of increased energy expenditure, animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery, and by enabling the anaerobic production of ATP. These low-oxygen responses are thought to be controlled universally across animals by the hypoxia-inducible factor (HIF). We find, however, that sponge and ctenophore genomes lack key components of the HIF pathway. Since sponges and ctenophores are likely sister to all remaining animal phyla, the last common ancestor of extant animals likely lacked the HIF pathway as well. Laboratory experiments show that the marine sponge Tethya wilhelma maintains normal transcription under oxygen levels down to 0.25% of modern atmospheric saturation, the lowest levels we investigated, consistent with the predicted absence of HIF or any other HIF-like pathway. Thus, the last common ancestor of all living animals could have metabolized aerobically under very low environmental oxygen concentrations.

Mitochondria and cellular oxygen sensing in the HIF pathway

2007 ◽  
Vol 409 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Cormac T. Taylor
Keyword(s):  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Oxygen Demand ◽  
Molecular Response ◽  
Diverse Range ◽  
Cellular Processes ◽  
Disease States ◽  
Final Electron ◽  
Cellular Oxygen ◽  
Hif Pathway

Mitochondrial respiration is responsible for more than 90% of oxygen consumption in humans. Cells utilize oxygen as the final electron acceptor in the aerobic metabolism of glucose to generate ATP which fuels most active cellular processes. Consequently, a drop in tissue oxygen levels to the point where oxygen demand exceeds supply (termed hypoxia) leads rapidly to metabolic crisis and represents a severe threat to ongoing physiological function and ultimately, viability. Because of the central role of oxygen in metabolism, it is perhaps not surprising that we have evolved an efficient and rapid molecular response system which senses hypoxia in cells, leading to the induction of an array of adaptive genes which facilitate increased oxygen supply and support anaerobic ATP generation. This response is governed by HIF (hypoxia-inducible factor). The oxygen sensitivity of this pathway is conferred by a family of hydroxylases which repress HIF activity in normoxia allowing its rapid activation in hypoxia. Because of its importance in a diverse range of disease states, the mechanism by which cells sense hypoxia and transduce a signal to the HIF pathway is an area of intense investigation. Inhibition of mitochondrial function reverses hypoxia-induced HIF leading to speculation of a role for mitochondria in cellular oxygen sensing. However, the nature of the signal between mitochondria and oxygen-sensing hydroxylase enzymes has remained controversial. In the present review, two models of the role for mitochondria in oxygen sensing will be discussed and recent evidence will be presented which raises the possibility that these two models which implicate ROS (reactive oxygen species) and oxygen redistribution respectively may complement each other and facilitate rapid and dynamic activation of the HIF pathway in hypoxia.

Reduction of acetylene by stationary cultures of free-living Rhizobium sp. under atmospheric oxygen levels

1976 ◽  
Vol 22 (7) ◽  
pp. 949-952 ◽  
Author(s):  
William R. Evans ◽  
Donald L. Keister
Keyword(s):  
Atmospheric Oxygen ◽  
Maximal Activity ◽  
Free Living ◽  
Oxygen Levels ◽  
Specific Activities ◽  
Rhizobium Sp ◽  
Oxygen Concentrations

The reduction of acetylene to ethylene by stationary (non-shaking) cultures of free-living rhizobia under atmospheric oxygen levels has been demonstrated. Under these conditions the development of the activity is inhibited by 10 mM NH4Cl and about 20% of oxygen is required for maximal activity. When the stationary cultures were shaken, oxygen concentrations of 1% and higher were found to be inhibitory. Specific activities of 20 and 40 nmol of acetylene reduced h−1 mg−1 protein were observed.

scholarly journals Induction of the HIF pathway: Differential regulation by chemical hypoxia and oxygen glucose deprivation

2019 ◽  
Author(s):  
Alicia E. Novak ◽  
Susan M. Jones ◽  
J. Paul Elliott
Keyword(s):  
Transcriptional Activation ◽  
Cellular Response ◽  
Target Genes ◽  
Expression Patterns ◽  
Hypoxia Inducible Factor ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Oxygen Levels ◽  
Chemical Hypoxia ◽  
Hif Pathway

AbstractThe Hypoxia Inducible Factor (HIF) proteins are the master regulators in the cellular response to varying oxygen levels, including hypoxia. The HIF complex is stabilized and accumulates when oxygen levels drop through inhibition of a degradative enzyme. An active HIF complex can act as a transcriptional regulator of hundreds of genes. In turn, these genes determine the response of the cell by inducing pathways which can promote survival, or result in cell death. However, little is known about the regulation of the transcriptional process. We were interested in learning more about the time dependence of transcriptional activation in order to target those pathways which could enhance cell survival after ischemia. Using mouse hippocampal organotypic cultures (HOTCs), we compared oxygen-glucose deprivation with the hypoxia mimetic cobalt, which inhibits the oxygen dependent prolyl hydroylase and blocks degradation of the HIF proteins. We demonstrated that two of the most studied HIF target genes (VEGF, EPO) as well as HIF structural genes show complex time and dose-dependent expression patterns in response to the two different insults. Understanding of these molecular responses is crucial for the development of future treatments to enhance recovery from hypoxia and stroke.

scholarly journals Hypoxia and Inflammation: Insights From High-Altitude Physiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathy Pham ◽  
Keval Parikh ◽  
Erica C. Heinrich
Keyword(s):  
High Altitude ◽  
Immune Function ◽  
Immune Cell ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Human Populations ◽  
Inflammatory Signaling ◽  
Time Domains ◽  
Inflammatory Phenotypes ◽  
Hif Pathway

The key regulators of the transcriptional response to hypoxia and inflammation (hypoxia inducible factor, HIF, and nuclear factor-kappa B, NF-κB, respectively) are evolutionarily conserved and share significant crosstalk. Tissues often experience hypoxia and inflammation concurrently at the site of infection or injury due to fluid retention and immune cell recruitment that ultimately reduces the rate of oxygen delivery to tissues. Inflammation can induce activity of HIF-pathway genes, and hypoxia may modulate inflammatory signaling. While it is clear that these molecular pathways function in concert, the physiological consequences of hypoxia-induced inflammation and how hypoxia modulates inflammatory signaling and immune function are not well established. In this review, we summarize known mechanisms of HIF and NF-κB crosstalk and highlight the physiological consequences that can arise from maladaptive hypoxia-induced inflammation. Finally, we discuss what can be learned about adaptive regulation of inflammation under chronic hypoxia by examining adaptive and maladaptive inflammatory phenotypes observed in human populations at high altitude. We aim to provide insight into the time domains of hypoxia-induced inflammation and highlight the importance of hypoxia-induced inflammatory sensitization in immune function, pathologies, and environmental adaptation.

scholarly journals Intermittent hypoxia enhances the expression of HIF1A by increasing the quantity and catalytic activity of KDM4A-C and demethylating H3K9me3 at the HIF1A locus

2021 ◽  
Author(s):  
Chloe-Anne Martinez ◽  
Neha Bal ◽  
Peter A Cistulli ◽  
Kristina M Cook
Keyword(s):  
Intermittent Hypoxia ◽  
Target Genes ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Sensing Systems ◽  
Cellular Oxygen ◽  
Fine Tune

Cellular oxygen-sensing pathways are primarily regulated by hypoxia inducible factor-1 (HIF-1) in chronic hypoxia and are well studied. Intermittent hypoxia also occurs in many pathological conditions, yet little is known about its biological effects. In this study, we investigated how two proposed cellular oxygen sensing systems, HIF-1 and KDM4A-C, respond to cells exposed to intermittent hypoxia and compared to chronic hypoxia. We found that intermittent hypoxia increases HIF-1 activity through a pathway distinct from chronic hypoxia, involving the KDM4A, -B and -C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A-C resulting in a decrease in H3K9 methylation. This contrasts with chronic hypoxia, which decreases KDM4A-C activity, leading to hypermethylation of H3K9. Demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia.

scholarly journals HIF Pathways in Clear Cell Renal Cancer

2021 ◽  
Author(s):  
Olivia Lombardi ◽  
David Robert Mole
Keyword(s):  
Cell Proliferation ◽  
Clear Cell ◽  
Hypoxia Inducible Factor ◽  
Von Hippel Lindau ◽  
Pathway Activation ◽  
Cellular Energetics ◽  
Cellular Oxygen ◽  
Immune Destruction ◽  
Hif Pathway ◽  
Cell Renal Cancer

Clear cell renal cancers (ccRCC) are characterized by inactivation of the VHL (von Hippel–Lindau) tumor suppressor. Work leading to the 2019 Nobel Prize for Physiology or Medicine has shown that this is central to cellular oxygen-sensing, orchestrated by the HIF (hypoxia-inducible factor) transcription factors. These regulate hundreds of genes that underpin many hallmarks of cancer, including angiogenesis, cellular energetics, cell proliferation, resisting cell death, and avoiding immune destruction. However, HIF also promotes processes that are detrimental to cancer cells. Therefore, the overall consequence of HIF pathway activation is a balance of these influences. We explore how variations in the HIF pathway during tumorigenesis alter this balance to promote ccRCC formation.

scholarly journals Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)

2006 ◽  
Vol 103 (26) ◽  
pp. 9814-9819 ◽  
Author(s):  
M. A. McDonough ◽  
V. Li ◽  
E. Flashman ◽  
R. Chowdhury ◽  
C. Mohr ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Cellular Oxygen

scholarly journals Oxygen Sensing and Viral Replication: Implications for Tropism and Pathogenesis

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1213
Author(s):  
Peter Jianrui Liu ◽  
Peter Balfe ◽  
Jane A McKeating ◽  
Mirjam Schilling
Keyword(s):  
Oxygen Tension ◽  
Cellular Response ◽  
Viral Infections ◽  
Oxygen Sensing ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Pharmaceutical Agents ◽  
Hif Pathway ◽  
Essential Prerequisite

The ability to detect and respond to varying oxygen tension is an essential prerequisite to life. Several mechanisms regulate the cellular response to oxygen including the prolyl hydroxylase domain (PHD)/factor inhibiting HIF (FIH)-hypoxia inducible factor (HIF) pathway, cysteamine (2-aminoethanethiol) dioxygenase (ADO) system, and the lysine-specific demethylases (KDM) 5A and KDM6A. Using a systems-based approach we discuss the literature on oxygen sensing pathways in the context of virus replication in different tissues that experience variable oxygen tension. Current information supports a model where the PHD-HIF pathway enhances the replication of viruses infecting tissues under low oxygen, however, the reverse is true for viruses with a selective tropism for higher oxygen environments. Differences in oxygen tension and associated HIF signaling may play an important role in viral tropism and pathogenesis. Thus, pharmaceutical agents that modulate HIF activity could provide novel treatment options for viral infections and associated pathological conditions.

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