Analysis of respiratory chain complex assembly in mitochondrial disorders

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Teikyo University (2014-2015); The University of Tokyo (2013)
• Principal Investigator: Mimaki Masakazu 帝京大学, 医学部, 教授 (40392419)
• Co-Investigator(Renkei-kenkyūsha): GOTO Yuichi 独立行政法人国立精神・神経医療研究センター, 疾病研究第二部, 部長 (20225668)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ミトコンドリア異常症 / 呼吸鎖複合体 / ミトコンドリアDNA / アセンブリーファクター / Blue Native電気泳動 / 遺伝 / 先天代謝異常

Outline of Final Research Achievements

To make a precise and correct diagnosis of mitochondrial disorders, we performed Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) using mitochondria derived from patients combined with analyses of DNA including mitochondrial DNA (mtDNA). We identified novel mtDNA mutations such as m.9155A>G mutation and nuclear DNA mutations such as POLG mutations in patients with mitochondrial respiratory chain disorders. As for common mtDNA mutations, such as the m.3243A>G mutation, we analyzed the impacts of the mutations on clinical features. We also investigated mitochondrial respiratory chain complex assembly process in the patient carrying FOXRED1 (FAD-dependent oxidoreductase domain-containing protein 1) mutations using BN-PAGE and our study revealed that FOXRED1 is a crucial component in the productive assembly of complex I. In conclusion, a combination of BN-PAGE and DNA analyses is useful and powerful to make prompt diagnoses of patients with mitochondrial disorders.

Free Research Field

小児神経学