Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis

Joon No Lee, Hyeonwoo Kim, Hongbing Yao, Yan Chen, Kayson Weng, Jin Ye

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)21424-21429
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
StatePublished - Dec 14 2010

Fingerprint

Unsaturated Fatty Acids
Triglycerides
Fatty Acids
Proteins
Diglycerides
Cultured Cells
Essential Fatty Acids
Trypsin
Cell Survival
Hot Temperature

Keywords

  • Diacylglyceride
  • Insig-1
  • Lipid droplet

ASJC Scopus subject areas

  • General

Cite this

Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis. / Lee, Joon No; Kim, Hyeonwoo; Yao, Hongbing; Chen, Yan; Weng, Kayson; Ye, Jin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 50, 14.12.2010, p. 21424-21429.

Research output: Contribution to journalArticle

@article{115be3c2390b4938b19688bdd4015eb0,
title = "Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis",
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.",
keywords = "Diacylglyceride, Insig-1, Lipid droplet",
author = "Lee, {Joon No} and Hyeonwoo Kim and Hongbing Yao and Yan Chen and Kayson Weng and Jin Ye",
year = "2010",
month = "12",
day = "14",
doi = "10.1073/pnas.1011859107",
language = "English (US)",
volume = "107",
pages = "21424--21429",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "50",

}

TY - JOUR

T1 - Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis

AU - Lee, Joon No

AU - Kim, Hyeonwoo

AU - Yao, Hongbing

AU - Chen, Yan

AU - Weng, Kayson

AU - Ye, Jin

PY - 2010/12/14

Y1 - 2010/12/14

N2 - 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.

AB - 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.

KW - Diacylglyceride

KW - Insig-1

KW - Lipid droplet

UR - http://www.scopus.com/inward/record.url?scp=78650718129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650718129&partnerID=8YFLogxK

U2 - 10.1073/pnas.1011859107

DO - 10.1073/pnas.1011859107

M3 - Article

VL - 107

SP - 21424

EP - 21429

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 50

ER -