2020 Fiscal Year Final Research Report
Molecular mechanism of organella homeostasis regulated by quantity and quality of lipids
| Project/Area Number |
18H04051
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
松坂 賢 筑波大学, 医学医療系, 教授 (70400679)
関谷 元博 筑波大学, 医学医療系, 准教授 (50420245)
韓 松伊 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (80729541)
中川 嘉 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | 多価不飽和脂肪酸 / 小胞体 / ミトコンドリア |
|---|
| Outline of Final Research Achievements |
SREBP and CREB3L3 are membrane-bound transcription factors involved in the maintenance of lipid metabolism in the liver. CREB3L3 deficiency results in the accumulation of nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs in the endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 promotes the formation of the SREBP-insulin induced gene 1 complex to suppress SREBPs for ER-Golgi transport, resulting in ER retention and inhibition of proteolytic activation at the Golgi and vice versa.
ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids into C18 species. Our study demonstrated that C18:0-ceramide suppresses hepatic insulin sensitivity and its production involves the formation of an Elovl6-ceramide synthase 4 (CerS4) complex in the endoplasmic reticulum and a Pnpla3-CerS4 complex on lipid droplets.
|
| Free Research Field |
内分泌・糖尿病
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、脂質制御による生体機能と病態の分子機序を、オルガネラレベルでの脂質の量と質の変化として捉え、その構造も含めた破綻（オルガネラ脂肪毒性）が病態の端緒となることを一部証明できた。本研究成果を踏まえ、今後さらに解析対象を様々な細胞オルガネラレベルに高度化し、エネルギー代謝、シグナル伝達、ストレス応答、増殖・分化など多様なバイオロジーにおいて、どのオルガネラの、どのリピッドが、どの分子をいかに制御しているか、ホメオスタシス（オルガネラリピッドコード）の共通原理を分子レベルで理解したい。
|
