Ferroptosis precedes apoptosis to facilitate specific death signalling by fatty acids

Abstract

Cell death is physiologically induced by specific mediators. However, our power to trigger the process in selected cells is quite limited. The protandric shrimp Hippolyte inermis offers a possible answer. Here, we analyse a de novo transcriptome of shrimp post-larvae fed on diatoms. The sex ratio of diatom-fed shrimps versus shrimps fed on control diets was dramatically altered, demonstrating the disruption of the androgenic gland, and their transcriptome revealed key modifications in gene expression. A wide transcriptomic analysis, validated by real-time qPCR, revealed that ferroptosis represents the primary factor to re-shape the body of this invertebrate, followed by further apoptotic events, and our findings open biotechnological perspectives for controlling the destiny of selected tissues. Ferroptosis was detected here for the first time in a crustacean. In addition, this is the first demonstration of a noticeable effect prompted by an ingested food, deeply impacting the gene networks of a young metazoan, definitely determining its future physiology and sexual differentiation.

Molecular Approaches Detect Early Signals of Programmed Cell Death in Hippolyte inermis Leach

“…This change is a consequence of a programmed cell-death (PCD) trigger directed selectively towards AG cells [ 24 , 25 ]. The chemical structure of the bioactive compound is still under investigation, but it is known to be a small lipophilic compound [ 26 ], probably similar to dihomo-γ-linolenic acid (DGLA) [ 27 ].…”

“…Molecular tools for H. inermis are, at present, very scarce, but Levy et al [ 30 ] have obtained transcriptomic libraries of representative development stages (immature, male, young female and mature female). However, previous studies [ 27 ] revealed a set of genes influenced by the ingestion of diatoms, demonstrating the remarkable role of ferroptosis as a form of PCD specifically acting on still undifferentiated gland tissues. This mechanism appears to be a smart physiologic strategy to produce massive changes in the physiology of an invertebrate by targeting a few young cells, and it has been demonstrated to be evolutionarily conserved, from Caenorabditis elegans to humans [ 27 ] and, of course, is present in the model shrimp H. inermis .…”

“…However, previous studies [ 27 ] revealed a set of genes influenced by the ingestion of diatoms, demonstrating the remarkable role of ferroptosis as a form of PCD specifically acting on still undifferentiated gland tissues. This mechanism appears to be a smart physiologic strategy to produce massive changes in the physiology of an invertebrate by targeting a few young cells, and it has been demonstrated to be evolutionarily conserved, from Caenorabditis elegans to humans [ 27 ] and, of course, is present in the model shrimp H. inermis . In this crustacean, several genes are activated by the ingestion of diatoms, and they are involved in ferroptosis of the AG, the apoptosis of the testes, and the activation of the IAG.…”

“…Remarkably, diatom ingestion triggers most physiological changes in young post-larvae just 5 days post-metamorphosis (PL5). In particular, it was demonstrated [ 27 ] that the whole process of sex reversal in this protandric species is completed within the first 2 weeks of post-larval development and that 5 days after the metamorphosis was the optimal stage at which to detect genic changes involved in the destruction of the AG and the consequent start of the ovary development, upon the feeding on diatoms. In the present experimental work, aimed at investigating the effects of natural compounds triggering PCD in selected shrimp tissues, an RNA extraction method was developed for the PL 5 stage.…”

“…Their expression levels were followed by real-time qPCR in PL 5 fed on Cocconeis spp., as compared to PL 5 fed on a basic feed (without diatoms). These data were compared with those obtained from the transcriptome [ 27 ] to investigate the physiological responses ruled by PCD and their functional relationships by means of interactomic analyses.…”