Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 21, Issue 17, Pages 2975-2986Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E09-02-0133
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [15GS0310, 20247026]
- Ono Medical Research Foundation
- Grants-in-Aid for Scientific Research [21390050, 22390061, 20247026, 15GS0310] Funding Source: KAKEN
Ask authors/readers for more resources
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates homeostatic responses collectively termed the unfolded protein response. Among the three principal signaling pathways operating in mammals, activating transcription factor (ATF)6 alpha plays a pivotal role in transcriptional induction of ER-localized molecular chaperones and folding enzymes as well as components of ER-associated degradation, and thereby mouse embryonic fibroblasts deficient in ATF6 alpha are sensitive to ER stress. However, ATF6 alpha-knockout mice show no apparent phenotype under normal growing conditions. In this report, we burdened mice with intraperitoneal injection of the ER stress-inducing reagent tunicamycin and found that wild-type mice were able to recover from the insult, whereas ATF6 alpha-knockout mice exhibited liver dysfunction and steatosis. Thus, ATF6 alpha-knockout mice accumulated neutral lipids in the liver such as triacylglycerol and cholesterol, which was ascribable to blockage of beta-oxidation of fatty acids caused by decreased mRNA levels of the enzymes involved in the process, suppression of very-low-density lipoprotein formation due to destabilized apolipoprotein B-100, and stimulation of lipid droplet formation resulting from transcriptional induction of adipose differentiation-related protein. Accordingly, the hepatocytes of tunicamycin-injected knockout mice were filled with many lipid droplets. These results establish links among ER stress, lipid metabolism, and steatosis.
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