Iron homeostasis is a vital process that balances access to free iron to fuel physiological processes with iron storage to reduce the deleterious aspects of excess free iron. Dysfunctional iron homeostasis can lead to iron overload, in which excess free iron can promote cellular injury, ferroptosis, and eventual organ damage as a result. The cellular consequences of long-term iron overload including the cellular pathways that lead to pathological changes or those that may provide protection against damage are incompletely defined. Here, we use dietary and genetically engineered mouse models of iron overload combined with mass spectrometry-based quantitative proteomics to determine the iron overload liver proteome. We identify and quantify over 8,000 proteins representing the most in-depth iron overload proteome evaluation to date. Using bioinformatics, we identify conserved upregulated pathways including ‘response to oxidative stress’ and downregulated pathways including ‘steroid homeostasis.’ Furthermore, we identify an unexpected role for NCOA4, an autophagy adaptor that targets ferritin for autophagic degradation during iron deprivation, during iron overload. This work highlights the importance of further investigation into NCOA4 and its role in diseases of iron overload. / 2025-01-30T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45524 |
| Date | 31 January 2023 |
| Creators | Dorman, Matthew J. |
| Contributors | Davies, Theresa, Mancias, Joseph |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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