MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis

被引:54
作者
Lee, Dongyeop [1 ,11 ]
An, Seon Woo A. [2 ]
Jung, Yoonji [2 ]
Yamaoka, Yasuyo [3 ]
Ryu, Youngjae [4 ,5 ]
Goh, Grace Ying Shyen [6 ]
Beigi, Arshia [6 ]
Yang, Jae-Seong [7 ]
Jung, Gyoo Yeol [7 ,8 ]
Ma, Dengke K. [9 ,10 ]
Ha, Chang Man [4 ,5 ]
Taubert, Stefan [6 ]
Lee, Youngsook [1 ,3 ]
Lee, Seung-Jae, V [2 ]
机构
[1] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, Gyeongbuk, South Korea
[2] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon, South Korea
[3] Pohang Univ Sci & Technol, Dept Integrat Biosci & Biotechnol, Pohang, Gyeongbuk, South Korea
[4] Korea Brain Res Inst, Res Div, Daegu, South Korea
[5] Korea Brain Res Inst, Brain Res Core Facil, Daegu, South Korea
[6] Univ British Columbia, Dept Med Genet, BC Childrens Hosp Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC, Canada
[7] Pohang Univ Sci & Technol, Dept Chem Engn, Pohang, Gyeongbuk, South Korea
[8] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang, Gyeongbuk, South Korea
[9] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[10] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[11] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA
基金
新加坡国家研究基金会; 加拿大健康研究院;
关键词
FATTY-ACID-COMPOSITION; C; ELEGANS; LIFE-SPAN; CAENORHABDITIS-ELEGANS; EXPRESSION ANALYSIS; MEDIATOR SUBUNIT; STRESS; METABOLISM; ACTIVATION; INHIBITION;
D O I
10.1371/journal.pbio.3000415
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.
引用
收藏
页数:28
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