한빛사 논문
Abstract
Joon No Leea,1, Hyeonwoo Kima,1, Hongbing Yaoa, Yan Chena,3, Kayson Wengb, and Jin Yea,2
aDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; and
bDepartment of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712
3Present address: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390
Edited* by Joseph L. Goldstein, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 20, 2010 (received for review August 9, 2010)
1J.N.L. and H.K. contributed equally to this work.
Abstract
Fatty acids (FAs) are essential for cell survival, yet their overaccumulation causes lipotoxicity. To prevent lipotoxicity, cells store excess FAs as triglycerides (TGs). In cultured cells TG synthesis is activated by excess unsaturated but not saturated FAs. Here, we identify Ubxd8 as a sensor for unsaturated FAs and regulator of TG synthesis. In cultured cells depleted of FAs, Ubxd8 inhibits TG synthesis by blocking conversion of diacylglycerols (DAGs) to TGs. Excess unsaturated but not saturated FAs relieve this inhibition. As a result, unsaturated FAs are incorporated into TGs, whereas saturated FAs are incorporated into DAGs. In vitro, unsaturated but not saturated FAs alter the structure of purified recombinant Ubxd8 as monitored by changes in its thermal stability, trypsin cleavage pattern, and oligomerization. These results suggest that Ubxd8 acts as a brake that limits TG synthesis, and this brake is released when its structure is altered by exposure to unsaturated FAs.
diacylglyceride, Insig-1, lipid droplet
Footnotes
2To whom correspondence should be addressed.
Author contributions: J.N.L. and J.Y. designed research; J.N.L., H.K., H.Y., Y.C., and K.W. performed research; J.N.L., H.K., H.Y., and J.Y. analyzed data; and J.N.L., H.K., H.Y., and J.Y. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1011859107/-/DCSupplemental.
Freely available online through the PNAS open access option.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기