Molecular mechanisms of a functional linkage between epigenome and mitochondria, and its pathophysiological association

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04707
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• 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): 2015-04-01 – 2018-03-31
• Keywords: エピゲノム / 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 regulatory mechanisms and molecules which functionally link between epigenome and mitochondria. Using specific siRNA libraries and some cell lines, we examined cellular phenotypes, molecular function, RNA-Seq and ChIP-Seq to identify target genes of epigenetic factors. Especially, the lysine methylase SETD8/PR-Set7, which mono-methylates H4K20, was involved in senescence-associated metabolic remodeling, by controlling expression of genes related to nucleolus and mitochondria in human fibroblasts. Further, the lysine demethylase LSD1, a nuclear enzyme which utilizes the flavin adenosine dinucleotide as a cofactor, regulated differentiation and energy metabolism in mouse myoblasts. Inhibition of LSD1 resulted in gene activation for slow twitch fiber differentiation and energy metabolism. These indicate that the epigenetic factors have an essential role in mitochondrial metabolism in various cellular types and conditions.

Free Research Field

エピジェネティクス