Evaluation of involvement in neurodegeneration by collapse of mitochondrial DNA maintenance mechanism using iPS cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15083
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Hiroshima University
• Principal Investigator: Morino Hiroyuki 広島大学, 原爆放射線医科学研究所, 准教授 (10397953)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 遺伝子 / 脳神経疾患 / ミトコンドリア

Outline of Final Research Achievements

We identified TWNK (C10orf2) as a new causative gene of Perrault syndrome. TWNK encodes mitochondrial DNA (mtDNA) helicase and is involved in mitochondrial maintenance mechanism. The purpose of this study is to reproduce the process of mutations of TWNK damaging the maintenance mechanism of mtDNA and leading to neuronal death by patient-derived iPS cells. Using the fact that mtDNA mutation is initialized when iPS cells are established, we observed the accumulation of mtDNA mutations in neurons differentiated from iPS cells. A cell-line that minimized mitochondrial abnormality was obtained and it was shown that mtDNA mutations accumutated due to TWNK mutations.

Free Research Field

神経内科