AI Article Synopsis
- Lipid droplets (LDs) are crucial for storing energy and maintaining lipid balance in cells, but their interaction with cellular metabolism, especially in the context of obesity, is not well-understood.
- A genome-wide screening identified approximately 550 genes that influence lipid storage in macrophages, including the transcription factor MLX, which plays a key role in metabolic regulation.
- When LDs accumulate, MLX and related factors bind to them, limiting their transcriptional activity and affecting glucose response; a lack of LDs leads to increased activity of MLX-regulated metabolic genes.
Article Abstract
Lipid droplets (LDs) store lipids for energy and are central to cellular lipid homeostasis. The mechanisms coordinating lipid storage in LDs with cellular metabolism are unclear but relevant to obesity-related diseases. Here we utilized genome-wide screening to identify genes that modulate lipid storage in macrophages, a cell type involved in metabolic diseases. Among ∼550 identified screen hits is MLX, a basic helix-loop-helix leucine-zipper transcription factor that regulates metabolic processes. We show that MLX and glucose-sensing family members MLXIP/MondoA and MLXIPL/ChREBP bind LDs via C-terminal amphipathic helices. When LDs accumulate in cells, these transcription factors bind to LDs, reducing their availability for transcriptional activity and attenuating the response to glucose. Conversely, the absence of LDs results in hyperactivation of MLX target genes. Our findings uncover a paradigm for a lipid storage response in which binding of MLX transcription factors to LD surfaces adjusts the expression of metabolic genes to lipid storage levels.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397554 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2020.01.014 | DOI Listing |
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