NRF3 upregulates gene expression in SREBP2-dependent mevalonate pathway with cholesterol uptake and lipogenesis inhibition
Tsuyoshi Waku, Toru Hagiwara, Natsuko Tamura, Yuri Atsumi, Yasuomi Urano, Mikiko Suzuki, Takuya Iwami, Katsuya Sato, Masayuki Yamamoto, Noriko Noguchi, Akira Kobayashi
Abstract
gene encoding an enzyme in the production of GGPP from farnesyl pyrophosphate (FPP), a lanosterol precursor. NRF3 overexpression also enhances cholesterol uptake through RAB5-mediated macropinocytosis process, a bulk and fluid-phase endocytosis pathway. Moreover, we find that GGPP treatment abolishes NRF3 knockdown-mediated increase of neutral lipids. These results reveal the potential roles of NRF3 in the SREBP2-dependent mevalonate pathway for cholesterol uptake through macropinocytosis induction and for lipogenesis inhibition through GGPP production.
Topics & Concepts
LanosterolLipogenesisMevalonate pathwayGene knockdownCholesterolCell biologyBiologySterol regulatory element-binding proteinBiochemistryMevalonic acidLipid metabolismOxysterolChemistrySterolBiosynthesisEnzymeGeneCholesterol and Lipid MetabolismPlant biochemistry and biosynthesisLipid metabolism and biosynthesis