Revealing the mechanism of mitochondrial localization in the sperm midpiece

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17852
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology); Integrative animal science
• Research Institution: Osaka University
• Principal Investigator: Keisuke Shimada 大阪大学, 微生物病研究所, 助教 (60779601)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ミトコンドリア鞘形成 / 精子形成

Outline of Final Research Achievements

We discovered that absence of Sperm mitochondria related gene 1(SMDR1) disrupts mitochondrial sheath formation, resulting in reduced sperm motility and male sterility. In vitro analysis demonstrates that SMDR1 induces mitochondrial clustering, revealing that SMDR1 functions as an adherence factor between mitochondria. In mouse testicular germ cells, SMDR1 localizes to the mitochondrial surface and directly interacts with mitochondrial outer membrane proteins VDAC2 and VDAC3 as well as SMDR2. These findings suggest that SMDR1 binds to VDAC proteins to tether adjacent mitochondria, and this tethering allows mitochondria to properly elongate and coil around the sperm flagellum. Thus, our studies demonstrate for the first time that SMDR1 regulates sperm mitochondrial dynamics, an essential function for mitochondrial sheath formation and male fertility.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

精子の中片部にはミトコンドリア鞘と呼ばれる特徴的な構造を有しており，ミトコンドリア鞘の形成不全は精子の運動性低下を引き起こし，雄性不妊の原因となる。現在までにこのミトコンドリア鞘形成に関わる分子メカニズムについては全く明らかになっておらず，これを解明することは将来的に雄性不妊の治療法や男性避妊薬の開発に繋がる可能性がある。さらにこのミトコンドリア鞘はミトコンドリアの様々な形態の変化が複合的に生じた結果形成されるものであり，このメカニズム解析は一般的なミトコンドリアダイナミクス研究へ応用される可能性がある。