SLC39A11 mediates intracellular manganese partitioning and adaptive iron transport.

Authors

Yanmei Cui, Fan Du, Juan Wang, Bing Zhou

Published in

Cell reports. Volume 45. Issue 8. Pages 117781. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Zrt/Irt-like protein (ZIP) family members typically mediate zinc transport into the cytoplasm. Here, we characterize SLC39A11(ZIP11)-an evolutionarily conserved ZIP homologous to Escherichia coli metal ZupT-revealing its context-dependent role in metal homeostasis. ZIP11 could remove Fe²⁺ from the endoplasmic reticulum (ER)/Golgi to the cytosol when ER/Golgi Fe²⁺ rises. This is relevant to fibrosis, where ZIP13 upregulation supports collagen synthesis and ZIP11 mitigates iron overload. Significantly, AAV8-mediated ZIP11 expression drastically suppresses CCl₄-induced liver fibrosis in mice, highlighting therapeutic potential. However, ZIP11 normally regulates Mn²⁺ partitioning between ER/Golgi and cytosol: its loss reduces ER/Golgi Mn²⁺, increases cytosolic Mn²⁺, and enhances manganese toxicity. ZIP11 and Mn²⁺ transporter TMEM165 double deficiency exacerbates Mn²⁺ sensitivity, indicating synergy between them. We therefore establish ZIP11 as an ER/Golgi Mn²⁺ transporter with Fe²⁺ transport plasticity and as an ER/Golgi-to-cytosol iron transporter that acts oppositely to ZIP13 to maintain optimal ER/Golgi iron levels.

PMID:
42531133
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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