Identification of organelle zone regulating host defense response

2021 Fiscal Year Final Research Report

• Project Area: Toward an integrative understanding of functional zones in organelles
• Project/Area Number: 17H06415
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University (2018-2021); The University of Tokushima (2017)
• Principal Investigator: Saitoh Tatsuya 大阪大学, 薬学研究科, 教授 (60456936)
• Co-Investigator(Kenkyū-buntansha): 森田 英嗣 弘前大学, 農学生命科学部, 准教授 (70344653) ; 印東 厚 徳島大学, 先端酵素学研究所(次世代), 助教 (70779058)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: オルガネラ / ウイルス / 細菌 / 免疫 / 炎症 / 細胞死 / タンパク質分解

Outline of Final Research Achievements

Organelles are involved in cellular activities that are fundamental to life, and each plays a highly specialized role. Organelles have sites for their function, and these sites are defined as organelle zones. In this study, we analyzed host defense responses from the viewpoint of organelle zones and made the following five findings. (1) The zone on the Golgi apparatus is involved in interferon production against DNA viruses. (2) The zone on the plasma membrane is involved in the inflammatory response induced by phagosome damage. (3) The molecule that recognizes zones of membrane damage caused by bacterial infection is involved in xenophagy. (4) The degradation zone in the virus replication organelle is involved in flavivirus replication. (5) The mitochondria - virus replication organelle contact zone is involved in viral replication.

Free Research Field

免疫学、生物系薬学

Academic Significance and Societal Importance of the Research Achievements

病原体に対する宿主応答に関しては、病原体成分を認識するセンサー、その下流のシグナル伝達因子、病原体複製に関わる因子が数多く同定されてきたが、宿主応答の時空間制御については不明な点が数多く残されていた。本研究はオルガネラ・ゾーンという独自の観点から新たな関連分子、制御メカニズム、生物学的意義などを見出したものであり、時空間制御の一端を明らかにしたという点で学術的意義がある。また、本研究は感染症において治療標的となり得る分子機構を明らかにしたものであり、新たな治療薬の開発に寄与するという点で社会的な意義がある。