Dissecting the function and regulation of mitochondrial quality control system using multi-matrixed screening assay

Research Project

Project/Area Number	26860063
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Pharmacology in pharmacy
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	Toshimori Kitami 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (70708594)
Project Period (FY)	2014-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	ミトコンドリア / スクリーニング / 炎症
Outline of Final Research Achievements	Decline in mitochondrial function is associated with variety of complex diseases including type 2 diabetes, neurodegenerative disease, and cardiovascular disease. Mitochondrial function is maintained at the level of abundance and quality. We sought to study the role of mitochondrial quality control in complex disease pathway called NLRP3 inflammasome. This pathway triggers the release of inflammatory cytokine and is involved in variety of complex diseases. We performed focused genetic over-expression and knockout screens to assess the impact of mitochondrial quality control genes on inflammatory phenotype. In addition, we performed genome-wide knockout screens for NLRP3 inflammasome activation to assess which mitochondrial genes are involved in this disease pathway. The results of the study will help clarify the role of mitochondria in inflammation as well as identify novel genes involved in regulating NLRP3 inflammasome.