Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis

Abstract 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...

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Autores principales:	Inês B. Santarino, Michelle S. Viegas, Neuza S. Domingues, Ana M. Ribeiro, Miguel P. Soares, Otília V. Vieira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/16c8045e1753486a9a8cdc9cdc113f47
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spelling	oai:doaj.org-article:16c8045e1753486a9a8cdc9cdc113f472021-12-02T16:08:00ZInvolvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis10.1038/s41598-017-05687-12045-2322https://doaj.org/article/16c8045e1753486a9a8cdc9cdc113f472017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05687-1https://doaj.org/toc/2045-2322Abstract 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.Inês B. SantarinoMichelle S. ViegasNeuza S. DominguesAna M. RibeiroMiguel P. SoaresOtília V. VieiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inês B. Santarino Michelle S. Viegas Neuza S. Domingues Ana M. Ribeiro Miguel P. Soares Otília V. Vieira Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
description	Abstract 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.
format	article
author	Inês B. Santarino Michelle S. Viegas Neuza S. Domingues Ana M. Ribeiro Miguel P. Soares Otília V. Vieira
author_facet	Inês B. Santarino Michelle S. Viegas Neuza S. Domingues Ana M. Ribeiro Miguel P. Soares Otília V. Vieira
author_sort	Inês B. Santarino
title	Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
title_short	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_sort	involvement of the p62/nrf2 signal transduction pathway on erythrophagocytosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/16c8045e1753486a9a8cdc9cdc113f47
work_keys_str_mv	AT inesbsantarino involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis AT michellesviegas involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis AT neuzasdomingues involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis AT anamribeiro involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis AT miguelpsoares involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis AT otiliavvieira involvementofthep62nrf2signaltransductionpathwayonerythrophagocytosis
_version_	1718384640470810624

Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis

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