Roles of mitochondrial iron homeostasis in development and progression of heart failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16016
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: SATO TATSUYA 札幌医科大学, 医学部, 助教 (40592473)
• Research Collaborator: Kikuchi Tatsuya
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ミトコンドリア / 鉄代謝 / 心不全

Outline of Final Research Achievements

Impaired mitochondrial iron homeostasis is known to lead to development of heart failure through increased oxidative stress. However, the details are still unclear because the way to evaluate distribution of cardiac mitochondrial iron has not been established. In this study, we examined how cardiac mitochondrial iron homeostasis is impaired in the models of heart failure by energy dispersive X-ray spectroscopy (EDS) using an aberration-corrected scanning electron microscope. Mice model of doxorubicin-induced cardiomyopathy showed increased mitochondrial iron content measured by biochemical Ferrozin assay. However, mapping of mitochondrial iron by EDS resulted in a rather small iron signal on the mitochondrial cristae and there was no iron accumulation in the mitochondria. The findings suggest that free iron, which catalyzes production of hydroxyl radicals, is increased and mitochondria-specific iron chelation is promising therapeutic target in doxorubicin-induced cardiomyopathy.

Free Research Field

循環器生理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、心筋ミトコンドリアにおける鉄恒常性の破綻を、収差補正走査型電子顕微鏡Titanを用いたエネルギー分散X線分光法 (EDS) により詳細に解析できる可能性が示唆された。これは、患者から得られた心筋生検標本に対しても応用が可能であることを意味する。今後は解析対象を患者心筋生検標本に拡大し、ミトコンドリア鉄恒常性の破綻が治療標的となりうる疾患像を明らかにすることで臨床への応用を目指し、更に研究を進めていく。