RRC ID 48890
Author Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV.
Title Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis.
Journal Sci Rep
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.
Volume 7(1)
Pages 5812
Published 2017-7-19
DOI 10.1038/s41598-017-05687-1
PII 10.1038/s41598-017-05687-1
PMID 28724916
PMC PMC5517431
MeSH Animals Autophagy Cell Line Erythrocytes / cytology* Erythrocytes / metabolism* Gene Expression Regulation Humans Intracellular Space / metabolism Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins NF-E2-Related Factor 2 / metabolism* Phagocytosis* Phagosomes / metabolism Phosphorylation Rabbits Sequestosome-1 Protein / metabolism* Signal Transduction* Ubiquitin / metabolism
IF 3.998
Times Cited 7
Mice RBRC01390