Research ArticlePhysiology

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

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Science Signaling  14 Apr 2015:
Vol. 8, Issue 372, pp. ra34
DOI: 10.1126/scisignal.aaa5903

Red cells need leucine to make hemoglobin

Inhibitors of the protein complex mTORC1 are used in the clinic, but they can cause anemia. Limitation of nutrients, such as amino acids, inhibits mTORC1 activity, which reduces protein synthesis by enhancing the activity of the translation inhibitor protein 4E-BP. The oxygen-carrying protein complex hemoglobin in red blood cells contains globin proteins, which have a particularly high percentage of leucine residues, leading Chung et al. to investigate the role of mTORC1 in hemoglobin production. Deficiency or inhibition of LAT3, an uptake transporter for l-leucine, prevented hemoglobin production in zebrafish and mouse red blood cells. Inadequate l-leucine uptake prevented the translation of globin-encoding transcripts. Thus, red cell function critically depends on leucine availability.

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