Molecular basis for the formation of the mitochondrial crista structure

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21413
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Yamagata University
• Principal Investigator: Tamura Yasushi 山形大学, 理学部, 教授 (50631876)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: ミトコンドリア / クリステ

Outline of Final Research Achievements

To elucidate molecular mechanisms of mitochondrial cristae membrane formation, we focused on the human orthologs of yeast Mgm1, Mdm35, and MICOS (OPA1, PRELID1-TRIAP1, and MICOS), which were found to be factors in the formation of yeast Mgm1, Mdm35, and MICOS. Specifically, we constructed single and double KO cells of these factors, and analyzed mitochondria and cristae structures by fluorescence and electron microscopy. The results showed that laminar cristae was decreased in OPA1-KO cells as reported in previous studies. Furthermore, we noticed that crista structures were almost completely absent in OPA1-Mic60 double knockout cells, . We will elucidate the crista formation mechanism by re-expressing the deleted genes to these cells and observing the process of crista remodeling.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアのクリステ膜は，ミトコンドリアのATP生産の効率化に必須の構造である。このクリステ膜構造が見つかってから長い年月が経っているが，このような特徴的な膜構造が形成されるメカニズムはほとんどわかっていない。今回，わたしたちが出芽酵母を用いた研究によって独自に発見したミトコンドリアクリスて形成因子を，ヒトの細胞を用いて解析し，出芽酵母で得られた知見を確認することができた。今後さらに研究をすすめることで，クリステ膜形成の謎が明らかにできれば，ミトコンドリアの機能が低下した疾患の治療法戦略などに貢献できると期待される。