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Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle
Neutrophils are predominantly glycolytic cells that derive little ATP from oxidative phosphorylation; however, they possess an extensive mitochondrial network and maintain a mitochondrial membrane potential. Although studies have shown neutrophils need their mitochondria to undergo apoptosis and reg...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832465/ https://www.ncbi.nlm.nih.gov/pubmed/34411229 http://dx.doi.org/10.1182/blood.2021011010 |
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author | Willson, Joseph A. Arienti, Simone Sadiku, Pranvera Reyes, Leila Coelho, Patricia Morrison, Tyler Rinaldi, Giulia Dockrell, David H. Whyte, Moira K. B. Walmsley, Sarah R. |
author_facet | Willson, Joseph A. Arienti, Simone Sadiku, Pranvera Reyes, Leila Coelho, Patricia Morrison, Tyler Rinaldi, Giulia Dockrell, David H. Whyte, Moira K. B. Walmsley, Sarah R. |
author_sort | Willson, Joseph A. |
collection | PubMed |
description | Neutrophils are predominantly glycolytic cells that derive little ATP from oxidative phosphorylation; however, they possess an extensive mitochondrial network and maintain a mitochondrial membrane potential. Although studies have shown neutrophils need their mitochondria to undergo apoptosis and regulate NETosis, the metabolic role of the respiratory chain in these highly glycolytic cells is still unclear. Recent studies have expanded on the role of reactive oxygen species (ROS) released from the mitochondria as intracellular signaling molecules. Our study shows that neutrophils can use their mitochondria to generate ROS and that mitochondrial ROS release is increased in hypoxic conditions. This is needed for the stabilization of a high level of the critical hypoxic response factor and pro-survival protein HIF-1α in hypoxia. Further, we demonstrate that neutrophils use the glycerol 3-phosphate pathway as a way of directly regulating mitochondrial function through glycolysis, specifically to maintain polarized mitochondria and produce ROS. This illustrates an additional pathway by which neutrophils can regulate HIF-1α stability and will therefore be an important consideration when looking for treatments of inflammatory conditions in which HIF-1α activation and neutrophil persistence at the site of inflammation are linked to disease severity. |
format | Online Article Text |
id | pubmed-8832465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88324652022-03-02 Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle Willson, Joseph A. Arienti, Simone Sadiku, Pranvera Reyes, Leila Coelho, Patricia Morrison, Tyler Rinaldi, Giulia Dockrell, David H. Whyte, Moira K. B. Walmsley, Sarah R. Blood Phagocytes, Granulocytes, and Myelopoiesis Neutrophils are predominantly glycolytic cells that derive little ATP from oxidative phosphorylation; however, they possess an extensive mitochondrial network and maintain a mitochondrial membrane potential. Although studies have shown neutrophils need their mitochondria to undergo apoptosis and regulate NETosis, the metabolic role of the respiratory chain in these highly glycolytic cells is still unclear. Recent studies have expanded on the role of reactive oxygen species (ROS) released from the mitochondria as intracellular signaling molecules. Our study shows that neutrophils can use their mitochondria to generate ROS and that mitochondrial ROS release is increased in hypoxic conditions. This is needed for the stabilization of a high level of the critical hypoxic response factor and pro-survival protein HIF-1α in hypoxia. Further, we demonstrate that neutrophils use the glycerol 3-phosphate pathway as a way of directly regulating mitochondrial function through glycolysis, specifically to maintain polarized mitochondria and produce ROS. This illustrates an additional pathway by which neutrophils can regulate HIF-1α stability and will therefore be an important consideration when looking for treatments of inflammatory conditions in which HIF-1α activation and neutrophil persistence at the site of inflammation are linked to disease severity. American Society of Hematology 2022-01-13 /pmc/articles/PMC8832465/ /pubmed/34411229 http://dx.doi.org/10.1182/blood.2021011010 Text en © 2022 by The American Society of Hematology This article is made available via the PMC Open Access Subset for unrestricted reuse and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. |
spellingShingle | Phagocytes, Granulocytes, and Myelopoiesis Willson, Joseph A. Arienti, Simone Sadiku, Pranvera Reyes, Leila Coelho, Patricia Morrison, Tyler Rinaldi, Giulia Dockrell, David H. Whyte, Moira K. B. Walmsley, Sarah R. Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title | Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title_full | Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title_fullStr | Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title_full_unstemmed | Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title_short | Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle |
title_sort | neutrophil hif-1α stabilization is augmented by mitochondrial ros produced via the glycerol 3-phosphate shuttle |
topic | Phagocytes, Granulocytes, and Myelopoiesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832465/ https://www.ncbi.nlm.nih.gov/pubmed/34411229 http://dx.doi.org/10.1182/blood.2021011010 |
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