Novel mitochondrial ribosomal genes are associated with mitochondrial disorders

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23954
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Juntendo University
• Principal Investigator: borna nurun nahar 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (30849609)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: Mitochondrial disease / Mitoribosome / OxPhos / ATP

Outline of Final Research Achievements

Mitochondria are essential organelles that produce ATP through the oxidative phosphorylation system (OxPhos). This study is focused on the identification of novel causative genes of mitochondrial disease. Our group has analyzed about 700 mitochondrial disease patients with whole-exome sequencing analysis. It predicted five novel candidate nuclear genes of the mitochondrial ribosomes. I attempted to validate whether three of these five genes are related to mitochondrial disease by mitochondrial functional assays, two genes were removed from the study due to unavailable samples. In this study, I performed genomic, expression, and functional analysis using samples derived patients for further clarifications of the variants. These results strongly suggest that these variants are causative for mitochondrial diseases. Since these genes have not been reported in mitochondrial diseases, this study potentially lead to identification of novel causative genes for mitochondrial diseases.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリア病は様々な臓器、年齢で発症する代謝疾患の一つであり、核・ミトコンドリアゲノム両方のバリアントが病因となりうる。現在までに根本的治療法は確立されておらず、発症の分子機構の解明は治療・診断双方の面から重要である。本研究課題では核にコードされたミトコンドリアリボソーム関連遺伝子が新規のミトコンドリア病原因遺伝子として強く示唆された。ミトコンドリア病原因遺伝子としてのミトコンドリアリボソーム関連遺伝子の報告例は未だ少なく、本研究課題の成果により、新たなミトコンドリア病発症機構の理解、それらを応用した新たな治療法・診断法への発展が期待される。