Related Experiment Video
Updated: Oct 16, 2025

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
NRF3 upregulates gene expression in SREBP2-dependent mevalonate pathway with cholesterol uptake and lipogenesis
Tsuyoshi Waku1, Toru Hagiwara2, Natsuko Tamura2
1Laboratory for Genetic Code, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
Abstract:
Lipids, such as cholesterol and fatty acids, influence cell signaling, energy storage, and membrane formation. Cholesterol is biosynthesized through the mevalonate pathway, and aberrant metabolism causes metabolic diseases. The genetic association of a transcription factor NRF3 with obesity has been suggested, although the molecular mechanisms remain unknown. Here, we show that NRF3 upregulates gene expression in SREBP2-dependent mevalonate pathway. We further reveal that NRF3 overexpression not only reduces lanosterol, a cholesterol precursor, but also induces the expression of the GGPS1 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.
Related Concept Videos
Regulation of Nuclear Protein Sorting
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of the Unfolded Protein Response
Cholesterol: Significance and Regulation
Considering cholesterol and...
Master Transcription Regulators
Co-activators and Co-repressors

