Analysis of mitochondrial iron accumulation mechanism on sideroblastic anemia model cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Kaneko Kiriko 岩手医科大学, 医学部, 講師 (10545784)
• Co-Investigator(Kenkyū-buntansha): 古山 和道 岩手医科大学, 医学部, 教授 (80280874) ; 鈴木 亘 岩手医科大学, 医学部, 助教 (90610395)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 鉄代謝 / ヘム合成系 / フェロトーシス

Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanisms of mitochondrial iron accumulation and ineffective hematopoiesis in congenital sideroblastic anemia.
RNA-seq analysis revealed that iron import in sideroblastic anemia model cells is not affected by iron accumulation or decreased heme synthesis, and that iron is at the same level of iron import as in wild-type cells. Thus, the results suggest that excess iron may accumulate in mitochondria in model cells with reduced heme synthesis capacity. The results of investigation of ferroptosis also suggest that under conditions of iron accumulation in sideroblastic anemia model cells, ferroptosis may occur more frequently than in wild-type cell lines.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、赤芽球系培養細胞における鉄蓄積機構の一端を明らかとした。赤芽球に鉄が蓄積する疾患において、鉄蓄積機構の解明は新たな治療法開発の一助となりうる。また、非赤芽球細胞と赤芽球細胞ではヘム合成系や鉄代謝において共通する機序も多く、近年、鉄蓄積やフェロトーシスが神経変性疾患や虚血性疾患に関与する報告があることから、鉄蓄積に関わる機序の解明はより幅広い疾患における治療法開発に寄与できる可能性が考えられる。