Analysis of the mechanism how iron is transported safely in cytoplasm

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23722
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Yanatori Izumi 名古屋大学, 医学系研究科, 助教 (40454847)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 鉄 / 鉄代謝 / 鉄シャペロン

Outline of Final Research Achievements

Iron is an essential but potentially hazardous bio-metal. Because of its ability to readily accept or donate electrons, iron is a valuable cofactor. However, iron is potentially toxic because it catalyzes the generation of reactive oxygen species. Despite its high abundance in nature, ferric iron is poorly bioavailable due to its exceedingly low solubility at physiological pH. Thus, the acquisition and usage of iron presents a considerable challenge to cells and organisms, which have evolved sophisticated mechanisms to satisfy their metabolic needs and concomitantly minimize the risk of toxicity.
The endoplasmic reticulum (ER) has a central role in lipid and protein biosynthesis, where some enzymes need iron as a cofactor. Previous study demonstrated that the metal transporter had an iron transport activity in fly but not in human. Thus, I investigated whether this transporter possessed an iron transport activity at ER membrane.

Free Research Field

代謝、分子生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、細胞の内外での鉄の動態については多くの研究がなされてきたが、細胞内でどのように鉄が輸送されているかについてはほとんど不明のままであった。近年、鉄による細胞・組織障害は広く知られるようになり、鉄を介した新たな細胞死・フェロトーシスに関する報告は急激に増加している。鉄が細胞障害を起こすメカニズムの詳細を明らかにする上で細胞内で鉄がどのように輸送され、各小器官へと輸送されているかを知ることは非常に重要な意味を持つ。また、本研究で注目した輸送体(A)の変異はヒトでも報告があり、今後の疾患の原因究明につながることが期待される。