The University of Tokyo · 생화학·유전·분자생물학
노코 교수의 연구실은 간세포 내 지질 대사 및 지질 유도성 ER 스트레스 반응(UPR)의 분자 기전을 중심으로 연구를 진행하고 있습니다. 특히 인지질(PI)이 지질 합성에 직접 기여하는 새로운 경로나 비타민 E 수송 단백질(α-TTP)이 지질 리포파운드와의 상호작용을 통해 기능하는 메커니즘을 규명하고 있습니다. 또한 산화된 인지질 제거에 관여하는 PAF-AH(II) 효소의 생리적 기능과 지질 조절이 대사성 질환에 미치는 영향을 연구하고 있습니다. 이와 같은 연구는 비알코올성 간지방증(NAFLD) 등 대사질환의 병태생리학적 이해와 치료 전략 개발에 기여하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
We found a novel pathway fueling triglyceride synthesis in hepatocytes, by a direct metabolic flow of PI into triglycerides. Our findings provide an insight into the pathogenesis and therapeutics of NAFLD.
α-Tocopherol (vitamin E) transfer protein (α-TTP) regulates the secretion of α-tocopherol from liver cells. Missense mutations of some arginine residues at the surface of α-TTP cause severe vitamin E deficiency in humans, but the role of these residues is unclear. Here, we found that wild-type α-TTP bound phosphatidylinositol phosphates (PIPs), whereas the arginine mutants did not. In addition, PIPs in the target membrane promoted the intermembrane transfer of α-tocopherol by α-TTP. The crystal
Vitamins are compounds that are essential for the normal growth, reproduction and functioning of the human body. Of the 13 known vitamins, vitamins A, D, E and K are lipophilic compounds and are therefore called fat-soluble vitamins. Because of their lipophilicity, fat-soluble vitamins are solubilized and transported by intracellular carrier proteins to exert their actions and to be metabolized properly. Vitamin A and its derivatives, collectively called retinoids, are solubilized by intracellul
The unfolded protein response (UPR) is an adaptive stress response that responds to the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) and that adjusts the protein-folding capacity to the needs of the cell. Perturbation of cellular lipids also activates the UPR. Lipid-induced UPR has attracted much attention because it is associated with the pathology of some metabolic diseases. However, how the lipid-induced UPR is activated remains unclear. We previously showe
Membrane phospholipids are susceptible to oxidation, which is involved in various pathological processes such as inflammation, atherogenesis, neurodegeneration, and aging. One enzyme that may help to remove oxidized phospholipids from cells is intracellular type II platelet-activating factor acetylhydrolase (PAF-AH (II)), which hydrolyzes oxidatively fragmented fatty acyl chains attached to phospholipids. Overexpression of PAF-AH (II) in cells or tissues was previously shown to suppress oxidativ
Altered cellular lipid composition activates the endoplasmic reticulum unfolded protein response (UPR), and UPR signaling effects important changes in lipid metabolism. Secondary effects on protein folding homeostasis likely contribute to UPR activation, but deletion of the unfolded protein stress-sensing luminal domain of the UPR transducers PERK and IRE1α does not abolish their responsiveness to lipid perturbation. This finding suggests that PERK and IRE1α also directly recognize the membrane
The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by dietary consumption of fatty acids such as saturated fatty acids and polyunsaturated fatty acids (PUFAs). Cells must adapt to changes in composition of membrane fatty acids by regulating lipid-metabolizing enzymes. In this study, we investigated how cells respond to loading with excess PUFAs, such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid.
