Research Results

A First Discovery in Eukaryotes

Unravelling the Mechanism of Iron Oxide Formation in VivoFY2026

photo:NEMOTO Michiko
NEMOTO Michiko (Professor, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University)
Fusion Oriented Research for Disruptive Science and Technology (FOREST)
Development of Innovative Technology to Convert Excess Iron in Cancer Cells into Iron Oxide (2022-2028)

Eukaryotes Produce Teeth Made of Magnetite, Stronger than Zirconia

A research group led by Professor Michiko Nemoto at Graduate School of Environmental, Life, Natural Science and Technology at Okayama University has made a new discovery involving the mechanism by which eukaryotes*1 produce magnetite, a type of iron oxide. Chitons*2, a type of mollusk, possess many teeth composed of magnetite on their feeding organ called a radula, and these teeth show higher abrasion resistance than zirconia, a highly durable ceramic material sometimes used as a diamond substitute. However, the mechanism by which magnetite teeth are formed in vivo had remained unclear. The research team discovered a novel protein named "RTMP1" in the chiton's teeth and demonstrated that this protein induces the formation of iron oxide on chitin fibers that form the structural framework of the teeth.

*1 Eukaryotes
A collective term for organisms with a nucleus in their cells. This includes humans, animals, plants, fungi, etc.

*2 Chiton
A mollusk that inhabits rocky coasts, with eight dorsal shell plates and teeth adapted for scraping algae from rocks

Chitons Form Magnetite Within Their Bodies

Organisms are capable of producing hard substances, such as bones and teeth, within their own bodies. Such substances are known as "biominerals," and most are made from calcium or silicon. However, certain organisms produce biominerals with iron as the main component. The chiton, which inhabits rocky coastal areas, possesses teeth composed of magnetite (Fe3O4). These teeth are stronger and more abrasion resistant than zirconia, also known as artificial diamond (Fig. 1).

Fig. 1 Chitons from the Seto Inland Sea (left) and their teeth (right)

Fig. 1 Chitons from the Seto Inland Sea (left) and their teeth (right)

However, the mechanisms that enabled the chiton, a eukaryote, to form magnetite in vivo had remained unclear. Furthermore, while iron is an essential element for organisms, excess iron is known to contribute to the onset of cancer and neurodegenerative diseases. Therefore, figuring out the mechanisms by which chitons ingest and regulate iron is anticipated to contribute to the development of new treatments and pharmaceuticals.

Protein "RTMP1" Induces Magnetite Formation

Identification of a protein specific to chiton teeth

The research group collected three species of chitons (Acanthopleura japonica, Acanthochitona achates, Placiphorella stimpsoni) from the Seto Inland Sea and performed gene expression analysis of their radula tissues. As a result, homologs of proteins previously identified in the magnetite teeth of Cryptochiton stelleri were found to be present in all examined chiton species. Among them, a novel protein unique to chitons was discovered and named "RTMP1" (Radular Teeth Matrix Protein 1).

RTMP1 and iron oxide coexist in the radular tissue

Chiton teeth are formed through the following stages: (1) formation of the chitin fiber framework, (2) influx of iron, (3) accumulation of low-crystalline iron oxide*3, and (4) crystallization into magnetite (Fig. 2, left). Staining the radular tissue with an antibody for RTMP1 revealed that RTMP1 was most abundant just before stage (3), and furthermore, RTMP1 was already localized in the same regions where low-crystalline iron oxide was later deposited on chitin fibers (Fig. 2, right).

*3 Low-crystalline iron oxide
Immature iron oxide whose crystal alignment is not yet organized. The state before conversion to magnetite.

Fig. 2 Formation process of chiton teeth (left) and locations where RTMP1 and low-crystalline iron oxide appeared (right)

Fig. 2 Formation process of chiton teeth (left) and locations where RTMP1 and low-crystalline iron oxide appeared (right)

RTMP1 induces iron oxide formation

To investigate the properties of RTMP1, the research group artificially produced RTMP1 using baker’s yeast, which is widely used in life sciences for recombinant protein expression. The resulting RTMP1 bound to chitin and also to iron ions. Furthermore, when chitin fibers bound with RTMP1 were immersed in an iron solution, iron oxide particles formed on the chitin fibers. These results demonstrated that RTMP1 directly induces the formation of iron oxide.

A New Approach to Metal Materials and Pharmaceutical Development

This research has revealed that RTMP1 is involved in the process by which magnetite, a type of iron oxide, is produced from iron. This differs significantly from conventional synthesis methods that require high-temperature processing or hazardous substances. Magnetite exhibits strong magnetism and is used in devices such as hard disk drives. Utilizing RTMP1 could enable the development of technologies that synthesize magnetic materials in ways that are safe and environmentally friendly. Moreover, the mechanism for forming metal oxides only in targeted areas seems highly applicable to electronic devices and sensor materials, opening new possibilities in material science. Furthermore, because excessive iron accumulation is known to be associated with cancer and neurodegenerative diseases, the understanding gained through this study on the iron regulatory mechanism mediated by RTMP1 is expected to become foundational knowledge in the pursuit of developing novel treatments for these diseases.

Keyword
Chitons, magnetite, biominerals
Article
“Radular teeth matrix protein 1 directs iron oxide deposition in chiton teeth”
DOI:10.1126/science.adu0043