Ferritin is regulated by a neuro-intestinal axis in the nematode Caenorhabditis elegans

• Published in: Redox biology 2020-01, Vol.28, p.101359, Article 101359
• Main Authors: Romero-Afrima, Leonor, Zelmanovich, Veronica, Abergel, Zohar, Zuckerman, Binyamin, Shaked, Maayan, Abergel, Rachel, Livshits, Leonid, Smith, Yoav, Gross, Einav
• Format: Article
• Language: English
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Cell Hypoxia; EGL-9; Ferritin; Ferritins - metabolism; ftn-1; Gene Expression Regulation - drug effects; HIF-1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Intestinal Mucosa - metabolism; Iron - metabolism; Nervous System - metabolism; Neuropeptides - metabolism; Oxygen - pharmacology; Oxygen sensing neurons; Research Paper; Soluble guanylate cyclases; VHL-1
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2019.101359

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. [Display omitted] •The expression of ferritin 1 (ftn-1) is tightly regulated by O2 tension.•O2-sensing neurons inhibit the expression of ftn-1 in the intestine at 21% O2.•Hydroxylated–HIF–1 inhibits the expression of ftn-1 at 21% O2.•ftn-1 is important for protecting against Pseudomonas aeruginosa bacteria.