In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe(-/-) mice (an established model of human HFE-hemochromatosis). ; This work was supported by National funds through Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência (PTDC/SAU-FCF/101177/2008, PTDC/BIM-MET/0739/2012 and SFRH/BPD/108207/2015), by FEDER funds through the COMPETE – Operational Competitiveness Programme (FCOMP-01-0124-FEDER-011062 and FCOMP-01-0124-FEDER-028447) and Project Norte-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by Reitoria da Universidade do Porto/Santander through PP-IJUP2011-122. ; info:eu-repo/semantics/publishedVersion