Imaging analysis of mechno-sensing in mitochondria of living cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19291
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Nagoya University
• Principal Investigator: KOBAYASHI Takeshi 名古屋大学, 医学系研究科, 講師 (40402565)
• Co-Investigator(Kenkyū-buntansha): 曽我部 正博 名古屋大学, 医学系研究科, 研究員 (10093428)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: ミトコンドリア / メカノバイオロジー / カルシウム / 機械刺激 / 細胞骨格

Outline of Final Research Achievements

Animal cell utilizes mechanosensors that sense and convert mechanical signals into biochemical signals. However, the details of those sensors or signals remain unclear. Recently mitochondria have been demonstrated to activate several intracellular signaling pathways upon mechanical stress. Therefore, we hypothesize that mitochondria can feel and respond to mechanical stress as mechanosensors. In this project, we try to verify our hypothesis and to investigate the mitochondrial signaling pathways upon mechanical stress. We found that cultured mesenchymal stem cells elevated mitochondrial calcium concentration in response to mechanical stress, resulting in increased mitochondrial ATP levels. Pharmacological studies showed that the activity of mechanosensitive channels activities was not essential to the changes in mitochondrial calcium concentration. These results support our hypothesis that mitochondria could sense mechanical stimuli and transduce them to biochemical signals.

Free Research Field

細胞生物学、生理学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアのメカニカルストレス感知機構は生体の各組織においても機能していると考えられ、特に、骨格筋ではそのメカノセンシング機構の破綻に伴い筋萎縮が誘導されていることが示唆されている。従って、本研究によって、メカノストレス負荷に誘導されるシグナルの欠落や変調により筋萎縮が起きるメカニズムを他の経路と区別して解析することが可能になり、廃用性筋萎縮の予防・治療方法の開発へつながる可能性がある。