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      Lessons from Comparison of Hypoxia Signaling in Plants and Mammals

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          Abstract

          Hypoxia is an important stress for organisms, including plants and mammals. In plants, hypoxia can be the consequence of flooding and causes important crop losses worldwide. In mammals, hypoxia stress may be the result of pathological conditions. Understanding the regulation of responses to hypoxia offers insights into novel approaches for crop improvement, particularly for the development of flooding-tolerant crops and for producing better therapeutics for hypoxia-related diseases such as inflammation and cancer. Despite their evolutionary distance, plants and mammals deploy strikingly similar mechanisms to sense and respond to the different aspects of hypoxia-related stress, including low oxygen levels and the resulting energy crisis, nutrient depletion, and oxidative stress. Over the last two decades, the ubiquitin/proteasome system and the ubiquitin-like protein SUMO have been identified as key regulators that act in concert to regulate core aspects of responses to hypoxia in plants and mammals. Here, we review ubiquitin and SUMO-dependent mechanisms underlying the regulation of hypoxia response in plants and mammals. By comparing and contrasting these mechanisms in plants and mammals, this review seeks to pinpoint conceptually similar mechanisms but also highlight future avenues of research at the junction between different fields of research.

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          Most cited references177

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          HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

          HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.
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            Nitric oxide synthases: regulation and function.

            Nitric oxide (NO), the smallest signalling molecule known, is produced by three isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and molecular oxygen as substrates and require the cofactors reduced nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). All NOS bind calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively expressed in central and peripheral neurons and some other cell types. Its functions include synaptic plasticity in the central nervous system (CNS), central regulation of blood pressure, smooth muscle relaxation, and vasodilatation via peripheral nitrergic nerves. Nitrergic nerves are of particular importance in the relaxation of corpus cavernosum and penile erection. Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, and tadalafil) require at least a residual nNOS activity for their action. Inducible NOS (NOS II) can be expressed in many cell types in response to lipopolysaccharide, cytokines, or other agents. Inducible NOS generates large amounts of NO that have cytostatic effects on parasitic target cells. Inducible NOS contributes to the pathophysiology of inflammatory diseases and septic shock. Endothelial NOS (eNOS, NOS III) is mostly expressed in endothelial cells. It keeps blood vessels dilated, controls blood pressure, and has numerous other vasoprotective and anti-atherosclerotic effects. Many cardiovascular risk factors lead to oxidative stress, eNOS uncoupling, and endothelial dysfunction in the vasculature. Pharmacologically, vascular oxidative stress can be reduced and eNOS functionality restored with renin- and angiotensin-converting enzyme-inhibitors, with angiotensin receptor blockers, and with statins.
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              Autophagy and the integrated stress response.

              Autophagy is a tightly regulated pathway involving the lysosomal degradation of cytoplasmic organelles or cytosolic components. This pathway can be stimulated by multiple forms of cellular stress, including nutrient or growth factor deprivation, hypoxia, reactive oxygen species, DNA damage, protein aggregates, damaged organelles, or intracellular pathogens. Both specific, stimulus-dependent and more general, stimulus-independent signaling pathways are activated to coordinate different phases of autophagy. Autophagy can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli, through dual regulation of autophagy and other stress responses by multifunctional stress signaling molecules, and/or through mutual control of autophagy and other stress responses. Thus, autophagy is a cell biological process that is a central component of the integrated stress response. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Plants (Basel)
                Plants (Basel)
                plants
                Plants
                MDPI
                2223-7747
                17 May 2021
                May 2021
                : 10
                : 5
                : 993
                Affiliations
                [1 ]Department of Biology, Maynooth University, W23 F2K6 Maynooth, Ireland; CATHERINE.DOORLY.2020@ 123456MUMAIL.IE
                [2 ]Kathleen Lonsdale Institute for Human Health Research, Maynooth University, W23 F2K8 Maynooth, Ireland
                Author notes
                Author information
                https://orcid.org/0000-0003-3548-8213
                Article
                plants-10-00993
                10.3390/plants10050993
                8157222
                34067566
                5c69f432-c7f8-489e-80c8-1e035b01e597
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 27 April 2021
                : 12 May 2021
                Categories
                Review

                hypoxia,plants,mammals,ubiquitin/proteasome system,sumo,n-degron pathway,nitric oxide

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