The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Yoshio Yamauchi's research lab focuses on cellular cholesterol homeostasis, with a central emphasis on the molecular mechanisms governing cholesterol and phospholipid transport, particularly through ATP-binding cassette transporter A1 (ABCA1). The lab investigates how ABCA1 regulates high-density lipoprotein (HDL) biogenesis, sterol sensing at the endoplasmic reticulum, and the interplay between lipid metabolism and disease, including cancer metabolism and Tangier disease. Key research directions include the roles of signaling pathways such as PI3K-Akt-mTOR and PKC in regulating SREBP transcription factors and lipid raft integrity in cancer cells, as well as the origin and function of extracellular vesicles in intercellular communication. The lab integrates cell biology, biochemistry, and molecular signaling to uncover fundamental mechanisms of lipid homeostasis and their implications in human disease.
Figures are computed from collected data and may differ slightly.
ATP-binding cassette transporter A1 (ABCA1) plays an essential role in the helical apolipoprotein-mediated assembly of high density lipoprotein, and the apolipoporteins stabilize ABCA1 against calpain-mediated degradation during the reaction ((2002) J. Biol. Chem. 277, 22426-22429). Protein kinase C (PKC) inhibitors suppressed both ABCA1 stabilization and cellular lipid release mediated by apolipoprotein A-I (apoA-I) but not ABCA1 increase by calpain inhibitors. The increase of ABCA1 and the cel
The lipogenic phenotype is a metabolic hallmark of cancer cells. Sterol regulatory element-binding proteins (SREBP) are key transcriptional factors to regulate biosynthesis of cholesterol and fatty acids. It has been poorly understood how the lipogenic phenotype in cancer cells is regulated and how it augments their malignant properties. Here we describe roles of the melanoma antigen ganglioside GD3 and phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR complex 1 (mTORC1) signaling in the regulation
Differential regulation has been suggested for cellular cholesterol and phospholipid release mediated by apolipoprotein A-I (apoA-I)/ABCA1. We investigated various factors involved in cholesterol mobilization related to this pathway. ApoA-I induced a rapid decrease of the cellular cholesterol compartment that is in equilibrium with the ACAT-accessible pool in cells that generate cholesterol-rich HDL. Pharmacological and genetic inactivation of ACAT enhanced the apoA-I-mediated cholesterol releas
Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and are present in the blood, their identity is poorly characterized <i>in vivo</i>, limiting the identification of their origin in the blood. Since skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined mar
Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol and phospholipid export to apolipoprotein A-I for the assembly of high density lipoprotein (HDL). Mutations in ABC
Cholesterol is a vital lipid molecule for mammalian cells, regulating fluidity of biological membranes, and serving as an essential constituent of lipid rafts. Mammalian cells acquire cholesterol from extracellular lipoproteins and from <i>de novo</i> synthesis. Cholesterol biosynthesis generates various precursor sterols. Cholesterol undergoes metabolic conversion into oxygenated sterols (oxysterols), bile acids, and steroid hormones. Cholesterol intermediates and metabolites have diverse and i
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