HADH, involved in mitochondrial fatty acid metabolism, regulates temperature acclimation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15141
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Osaka University (2023); Konan University (2021-2022)
• Principal Investigator: Okahata Misaki 大阪大学, 大学院生命機能研究科, 特別研究員(RPD) (20880561)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: C. elegans / 高温馴化

Outline of Final Research Achievements

To elucidate the mechanism by which animals acclimate to temperature changes, we analyzed temperature acclimation of C. elegans. We screened for genes whose expression was altered by temperature change with RNA sequencing analysis. We focused on hadh gene, which is upregulated upon temperature increase. HADH is known to be involved in β-oxidation of fatty acid metabolism in mitochondria in humans, but it has not been reported to be involved in temperature response. The hadh mutant showed abnormal temperature acclimation with slower acclimation to 25°C compared to the wild-type animals. To identify tissues in which HADH regulates temperature acclimation, we performed expression analysis and tissue-specific rescue experiments. HADH was expressed in the intestine and some neurons. Abnormal temperature acclimation in hadh mutants was restored by expressing the wild-type hadh gene in neurons, suggesting that hadh regulate temperature acclimation by functioning in neurons.

Free Research Field

遺伝学

Academic Significance and Societal Importance of the Research Achievements

温度は常に存在する重要な環境情報であり、動物は温度変化に適応する生体メカニズムを備えている。体温調節機能の異常は熱中症やヒートショックなどを引き起こすことから、温度に馴れる仕組みを明らかにすることにより、温度に関わる疾患の解明につながると考えられる。本研究では、モデル動物である線虫C. elegansを用いた温度応答解析から、ミトコンドリアの脂肪酸代謝に関わるHADHが神経系で温度応答を制御することを明らかにした。HADHが温度応答に関わるという報告は本研究によって初めて明らかになったことから、今後解析を進めることにより、温度応答に関わる新規メカニズムの解明が期待される。