Molecular Responses to Hypoxia-Inducible Factor 1<i>α</i> and Beyond

Brocato, Jason; Chervona, Yana; Costa, Max

doi:10.1124/mol.113.089623

Cited by 109 publications

(96 citation statements)

References 79 publications

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“…It regulates the genes transcription in response to hypoxia (Brocato et al, 2014). This HIF consists of a heterodimer of an a subunit that is oxygen-regulated, and a constitutive b subunit that is oxygen-independent (Semenza, 2013).…”

Section: Autophagy Hypoxia and Hifmentioning

confidence: 99%

Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells

Fang

Tan

Zhang

2015

Cell Biology International

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Section: Autophagy Hypoxia and Hifmentioning

confidence: 99%

Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells

Fang

Tan

Zhang

2015

Cell Biology International

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“…Overall, HIF-α and PHD mRNA and protein expression were modulated in a oxygen-dependent manner with comparable trends suggesting a possible supplemental role of transcriptional activation in addition to post-translational control mechanisms that are well characterized in mammalian models (Brocato et al 2014).…”

Section: Discussionmentioning

confidence: 90%

Hypoxia-Inducible Factor α and Hif-prolyl Hydroxylase Characterization and Gene Expression in Short-Time Air-Exposed Mytilus galloprovincialis

et al. 2015

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Aquatic organisms experience environmental hypoxia as a result of eutrophication and naturally occurring tidal cycles. Mytilus galloprovincialis, being an anoxic/hypoxic-tolerant bivalve, provides an excellent model to investigate the molecular mechanisms regulating oxygen sensing. Across the animal kingdom, inadequacy in oxygen supply is signalled predominantly by hypoxia-inducible factors (HIF) and Hif-prolyl hydroxylases (PHD). In this study, hif-α 5'-end and partial phd mRNA sequences from M. galloprovincialis were obtained. Phylogenetic and molecular characterization of both HIF-α and PHD putative proteins showed shared key features with the respective orthologues from animals strongly suggesting their crucial involvement in the highly conserved oxygen sensing pathway. Both transcripts displayed a tissue-specific distribution with prominent expression in gills. Quantitative gene expression analysis of hif-α and phd mRNAs from gills of M. galloprovincialis demonstrated that both these key sensors are transcriptionally modulated by oxygen availability during the short-time air exposure and subsequent re-oxygenation treatments proving that they are critical players of oxygen-sensing mechanisms in mussels. Remarkably, hif-α gene expression showed a prompt and transient response suggesting the precocious implication of this transcription factor in the early phase of the adaptive response to hypoxia in Mytilus. HIF-α and PHD proteins were modulated in a time-dependent manner with trends comparable to mRNA expression patterns, thus suggesting a central role of their transcriptional regulation in the hypoxia tolerance strategies in marine bivalves. These results provide molecular information about the effects of oxygen deficiency and identify hypoxia-responsive biomarker genes in mussels applicable in ecotoxicological studies of natural marine areas.

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“…Thus, it is not surprising that several lines of evidence support a role for HIF-1 in the interplay between mitochondria, metabolism, and stem cell functions. As HIF-1 is involved in the dedifferentiation of cancer cells [69], it might also regulate differentiation pathways in pathological conditions.…”

Section: Oxygen Sensing and The Hif Pathwaymentioning

confidence: 99%

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Wanet

Arnould

Najimi

et al. 2015

Stem Cells and Development

260

216

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As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases.

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Molecular Responses to Hypoxia-Inducible Factor 1α and Beyond

Cited by 109 publications

References 79 publications

Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells

Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells

Hypoxia-Inducible Factor α and Hif-prolyl Hydroxylase Characterization and Gene Expression in Short-Time Air-Exposed Mytilus galloprovincialis

Connecting Mitochondria, Metabolism, and Stem Cell Fate

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