Abdelghani Mazouzi: SMIM1 Links Hemoglobin Internalization to Cellular Iron Metabolism
Abdelghani Mazouzi, Postdoctoral Research Fellow at The Netherlands Cancer Institute, shared Thijn Brummelkamp’s post on LinkedIn:
“If you like high-resolution genetic screens and metabolism, this post is for you!
I am very excited to share our new bioRxiv preprint, describing work I did during my postdoc in the lab of Thijn Brummelkamp at The Netherlands Cancer Institute!
We developed a powerful approach for FACS-based gain-of-function genetic screens using molecular readouts across diverse biological processes.
Using this strategy, we identified SMIM1, a fascinating 78-amino-acid protein, as a regulator of iron metabolism through a previously unknown pathway for cellular iron uptake.
We found that SMIM1 directly binds hemoglobin and promotes its internalization through clathrin-dependent endocytosis, allowing cells to acquire iron independently of the canonical transferrin receptor pathway.
Importantly, genetic variants in SMIM1 influence hemoglobin levels and erythrocyte traits in humans.
SMIM1-deficient mice display iron deficiency in early erythroid precursors under conditions of erythropoietic stress, highlighting the physiological relevance of this pathway.
I am extremely excited about these findings and the tools we now have in hand for identifying new biology.
I would like to thank all the co-authors for their help and support with this work, and I am very curious to hear your thoughts!”
Thijn Brummelkamp, Director of Research at The Netherlands Cancer Institute, Professor of Experimental Genetics at Universitair Medisch Centrum Utrecht, shared a post on LinkedIn about a recent article he and his colleagues co-authored, published in bioRxiv, adding:
“Our group uses genetics to identify what we call ‘alternative cellular pathways’.
This led to the identification of SLFN-induced ribosome stalling as an alternative pathway for DNA damage-induced apoptosis and DIESL–TMX1 as an alternative pathway for triglyceride synthesis.
We are now excited to share a new preprint describing SMIM1 as an alternative pathway for cellular iron uptake, through the uptake of haemoglobin.
This project was led by Abdelghani Mazouzi, combining both gain- and loss-of-function genetics.
Proud to share that Abdel will soon start his own lab.
Congratulations, Abdel!”
Title: SMIM1 drives an alternative iron uptake pathway
Authors: Abdelghani Mazouzi, Daniëlle Bianchi, Catrin Lutz, Sarah C. Moser, Guizela Huelsz-Prince, Onno B Bleijerveld, Bim de Klein, Serge Scheffers, Marleen Dekker, Maarten L. Hekkelman, Hendrik A Messal, Alexander Fish, Lodewyk F A Wessels, Jos Jonkers, Thijn R. Brummelkamp
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