Molecular mechanisms and physiological roles for selective degradation of paternal mitochondria

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02435
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Gunma University
• Principal Investigator: SATO Miyuki 群馬大学, 生体調節研究所, 教授 (70321768)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: オートファジー / ミトコンドリア / 母性遺伝 / 線虫C.elegans

Outline of Final Research Achievements

In Caenorhabditis elegans embryos, paternally provided organelles, including mitochondria, are eliminated by selective autophagy, and this serves as the mechanism by which mitochondrial DNA is inherited maternally. We further identified an autophagy adaptor ALLO-1 that controls this process. ALLO-1 localizes on the paternal organelles very shortly after fertilization and this localization depends on its C-terminal region. We also found that ALLO-1 physically interacts with not only LGG-1, the worm homolog of LC3/ATG8 family, but also a component of the ATG1 complex. ALLO-1 is also required for recruitment of the ATG1 complex on the substrates. Our results suggest that this ALLO-1-dependent recruitment of the ATG1 complex could explain how the autophagosome formation is initiated on substrates.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアDNAの母性遺伝の仕組みは生物学の長年の謎であったが、オートファジーによって父性ミトコンドリアが選択的に分解されることが明らかとなった。次の課題は、「どのように父性ミトコンドリアだけが識別されるのか」という点である。本研究により選択性を決める鍵分子であるALLO-1の機能について理解が進み、標的周囲にオートファゴソーム膜を形成させる仕組みを明らかにした。また、この仕組みは線虫だけでなく哺乳類の選択的オートファジーとも類似性があり、種を超えて保存された仕組みであることも示唆された。