Study of the Pathological Significance of Enlarged Mitochondria in BOLA3 Mutations Using iPSCs.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15397
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Jichi Medical University
• Principal Investigator: Tokuyama Takeshi 自治医科大学, 医学部, 助教 (30808093)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: ミトコンドリア / ミトコンドリア心筋症 / ミトコンドリアダイナミクス / 疾患iPS細胞 / ミトコンドリア創薬 / BOLA3

Outline of Final Research Achievements

Mitochondrial functions are regulated in various ways, one of which is through the modulation of mitochondrial morphology. By observing fibroblasts derived from mitochondrial cardiomyopathy, we discovered an abnormal swollen morphology in some mitochondria, which we named Mito-Ball. We investigated its physiological significance. Mito-Balls were found to contain high levels of ATP and ROS, with a structure suggesting aggregation of the matrix and internal mitochondrial components. We also identified methods to reduce the presence of these structures. Future experiments using mice are anticipated to develop therapies using Mito-Balls as indicators.

Free Research Field

病態生理学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアの機能異常はアルツハイマー病・肥満・糖尿病・ 不妊など多岐にわたる疾患の病態基盤であると考えられている。今回観察されたMito-Ballは遺伝子変異箇所などによらず広範な細胞で観察されるもので、Mito-Ballはミトコンドリア障害においてユビキタスな現象であると考えられる。このことから、Mito-Ballに着目した研究成果はミトコンドリアを原因とする多くの病気の病態解明・治療法確立に役立つ知見になることが期待される。