Analysis of nucleolus-mitochondria network regulated by epigenetic factors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02618
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kumamoto University
• Principal Investigator: NAKAO MITSUYOSHI 熊本大学, 発生医学研究所, 教授 (00217663)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エピゲノム / 核小体 / ミトコンドリア / 遺伝子 / クロマチン / 代謝

Outline of Final Research Achievements

This study focuses on investigating novel epigenomic mechanisms which functionally link between nucleolus and mitochondria. Using specific siRNAs libraries, we found about 15 epigenetic factors that are involved in structure and function of nucleolus and mitochondria, and identified their target genes by RNA-seq and ChIP-seq. NSD2/WHSC1/MMSET methylase maintains growth-promoting gene activities to protect cellular senescence. In addition, we proposed the phenotypic variation in cellular senescence condition in fibroblasts. Further, LSD1/KDM1A and LSD2/KDM1B demethylases, nuclear enzymes that utilize the flavin adenosine dinucleotide as a cofactor, regulated energy metabolism in myocyte and adipocyte differentiation, respectively. Our findings indicate that these epigenetic factors have an essential role in controlling nucleolus and mitochondria metabolism.

Free Research Field

医化学関連

Academic Significance and Societal Importance of the Research Achievements

細胞の代謝の恒常性には、エネルギー（ATP）の合成と消費のバランスが重要である。その大半は、細胞質側のミトコンドリアでATPが合成され、核側の核小体によるリボソーム形成とタンパク質合成でATPが消費されている。このバランスを制御する機序については不明な点が多い。核小体とミトコンドリアの連動性に着目し、新規のエピゲノム制御機構を明らかにすることを目指した。核小体－ミトコンドリアのネットワークの基軸解明に迫り、生理と病態への関わりを明らかにするという学術的・社会的な意義がある。