Ferritin is regulated by a neuro-intestinal axis in the nematode Caenorhabditis elegans
Leonor Romero-Afrima,
Veronica Zelmanovich,
Zohar Abergel,
Binyamin Zuckerman,
Maayan Shaked,
Rachel Abergel,
Leonid Livshits,
Yoav Smith,
Einav Gross
Affiliations
Leonor Romero-Afrima
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Veronica Zelmanovich
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Zohar Abergel
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Binyamin Zuckerman
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Maayan Shaked
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Rachel Abergel
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Leonid Livshits
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel
Yoav Smith
Genomic Data Analysis Unit, The Hebrew University - Hadassah Medical School, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel
Einav Gross
Dept. of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. P.O. Box 12271, Jerusalem, 9112102, Israel; Corresponding author. Dept. of Biochemistry & Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12271, Jerusalem, 9112102, Israel.
Iron is vital for the life of most organisms. However, when dysregulated, iron can catalyze the formation of oxygen (O2) radicals that can destroy any biological molecule and thus lead to oxidative injury and death. Therefore, iron metabolism must be tightly regulated at all times, as well as coordinated with the metabolism of O2. However, how is this achieved at the whole animal level is not well understood. Here, we explore this question using the nematode Caenorhabditis elegans. Exposure of worms to O2 starvation conditions (i.e. hypoxia) induces a major upregulation in levels of the conserved iron-cage protein ferritin 1 (ftn-1) in the intestine, while exposure to 21% O2 decreases ftn-1 level. This O2-dependent inhibition is mediated by O2-sensing neurons that communicate with the intestine through neurotransmitter and neuropeptide signalling, and requires the activity of hydroxylated HIF-1. By contrast, the induction of ftn-1 in hypoxia appears to be HIF-1-independent. This upregulation provides protection against Pseudomonas aeruginosa bacteria and oxidative injury. Taken together, our studies uncover a neuro-intestine axis that coordinates O2 and iron responses at the whole animal level. Keywords: Ferritin, ftn-1, Hypoxia, Caenorhabditis elegans, HIF-1, EGL-9, VHL-1, Soluble guanylate cyclases, Oxygen sensing neurons
