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Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis

Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy...

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Autores principales: Santarino, Inês B., Viegas, Michelle S., Domingues, Neuza S., Ribeiro, Ana M., Soares, Miguel P., Vieira, Otília V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517431/
https://www.ncbi.nlm.nih.gov/pubmed/28724916
http://dx.doi.org/10.1038/s41598-017-05687-1
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author Santarino, Inês B.
Viegas, Michelle S.
Domingues, Neuza S.
Ribeiro, Ana M.
Soares, Miguel P.
Vieira, Otília V.
author_facet Santarino, Inês B.
Viegas, Michelle S.
Domingues, Neuza S.
Ribeiro, Ana M.
Soares, Miguel P.
Vieira, Otília V.
author_sort Santarino, Inês B.
collection PubMed
description Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process. In bone marrow-derived macrophages (BMDM) silenced for p62, RBC degradation is inhibited. P62, is also required for nuclear translocation and activation of the transcription factor Nuclear factor E2-related Factor 2 (NRF2) during erythrophagocytosis. Deletion of the Nrf2 allele reduces p62 expression and compromises RBC degradation. In conclusion, we reveal that erythrophagocytosis relies on an interplay between p62 and NRF2, potentially acting as protective mechanism to maintain reactive oxygen species at basal levels and preserve macrophage homeostasis.
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spelling pubmed-55174312017-07-20 Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis Santarino, Inês B. Viegas, Michelle S. Domingues, Neuza S. Ribeiro, Ana M. Soares, Miguel P. Vieira, Otília V. Sci Rep Article Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process. In bone marrow-derived macrophages (BMDM) silenced for p62, RBC degradation is inhibited. P62, is also required for nuclear translocation and activation of the transcription factor Nuclear factor E2-related Factor 2 (NRF2) during erythrophagocytosis. Deletion of the Nrf2 allele reduces p62 expression and compromises RBC degradation. In conclusion, we reveal that erythrophagocytosis relies on an interplay between p62 and NRF2, potentially acting as protective mechanism to maintain reactive oxygen species at basal levels and preserve macrophage homeostasis. Nature Publishing Group UK 2017-07-19 /pmc/articles/PMC5517431/ /pubmed/28724916 http://dx.doi.org/10.1038/s41598-017-05687-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Santarino, Inês B.
Viegas, Michelle S.
Domingues, Neuza S.
Ribeiro, Ana M.
Soares, Miguel P.
Vieira, Otília V.
Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_full Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_fullStr Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_full_unstemmed Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_short Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_sort involvement of the p62/nrf2 signal transduction pathway on erythrophagocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517431/
https://www.ncbi.nlm.nih.gov/pubmed/28724916
http://dx.doi.org/10.1038/s41598-017-05687-1
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