Study on molecular mechanisms of the interplay between endoplasmic reticulum dynamics and metabolic reprogramming

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Yamamoto Yasunori 神戸大学, 医学研究科, 准教授 (30467659)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 小胞体 / Three-way junction / リン酸化 / TMCC3 / 14-3-3 / 小胞体ストレス / Akt

Outline of Final Research Achievements

Cells cope with various stresses through metabolic reprogramming. While the endoplasmic reticulum (ER) is an organelle that plays central roles in regulation of cellular homeostasis, it remains unclear whether the ER is involved in metabolic reprogramming. In this study, we revealed TMCC3, an ER membrane protein, bound to the adaptor protein that mediated metabolic reprogramming, thereby regulating the ER morphology. We found that the protein level of TMCC3 was reduced in response to ER stress, leading to morphological change of the ER. We furthermore revealed that TMCC3 physically and functionally connect activation of the signaling molecule that drove metabolic reprogramming to morphological change of the ER.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

小胞体と代謝リプログラミングとの機能関係は不明であったが、本研究により、小胞体の形態変化がTMCC3を介して代謝リプログラミング調節分子と物理的にも機能的にも連結していることを示した点で学術的意義が大きい。TMCC3の発現上昇はがんの悪性度と密接に関わることが知られている。したがって、本研究で明らかにしたTMCC3による小胞体の形態変化と代謝リプログラミング制御ががんの悪性化を推進している可能性が考えられ、本研究成果は社会的にも意義が大きい。