Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis

I.B. Santarino, M.S. Viegas, N.S. Domingues, A.M. Ribeiro, M.P. Soares, O.V. Vieira

Research output: Contribution to journalArticle

7 Citations (Scopus)
134 Downloads (Pure)

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. © 2017 The Author(s).
Original languageEnglish
Pages (from-to)Online
Number of pages16
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 19 Jul 2017

Fingerprint Dive into the research topics of 'Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis'. Together they form a unique fingerprint.

  • Cite this