Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 30, Issue 3, Pages 793-805Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01327-09
Keywords
-
Categories
Funding
- CIHR
- NSERC
- AHFMR
- AIF
- CFI
Ask authors/readers for more resources
All eukaryotic cells have to maintain cholesterol concentrations within defined margins in order to function normally. Perturbing cholesterol homeostasis can result in a wide range of cellular and systemic defects, including cardiovascular diseases, as well as Niemann-Pick and Tangier diseases. Here, we show that DHR96 is indispensable for mediating the transcriptional response to dietary cholesterol and that it acts as a key regulator of the Niemann-Pick type C gene family, as well as of other genes involved in cholesterol uptake, metabolism, and transport. DHR96 mutants are viable and phenotypically normal on a standard medium but fail to survive on diets that are low in cholesterol. DHR96 mutants have aberrant cholesterol levels, demonstrating a defect in maintaining cholesterol homeostasis. Remarkably, we found that a high-cholesterol diet phenocopied the genomic profile of the DHR96 mutation, indicating that DHR96 resides at the top of a genetic hierarchy controlling cholesterol homeostasis in insects. We propose a model whereby DHR96 is activated when cellular cholesterol concentrations drop below a critical threshold in order to protect cells from severe cholesterol deprivation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available