Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.
Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.
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DOI：
10.1016/j.cell.2015.04.026
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发表时间：
2015-05-21
期刊：
影响因子：
64.5
通讯作者：
Horvitz HR
中科院分区：
文献类型：
--
作者：
Ma DK;Li Z;Lu AY;Sun F;Chen S;Rothe M;Menzel R;Sun F;Horvitz HR
细胞通过调节脂质去饱和和膜流动性来适应温度变化。这一基本过程发生在几乎所有形式的生命中，但其在真核生物中的机制尚不清楚。我们发现进化保守的C.线虫基因acdh-11（酰基-CoA-脱氢酶，ACDH）通过调节脂质去饱和酶FAT-7促进热适应。人类ACDH缺乏导致最常见的脂肪酸氧化遗传性疾病，其综合征因体温过高而加重。热上调acdh-11的表达以降低fat-7的表达。我们解决了ACDH-11的高分辨率晶体结构，并建立了其选择性和高亲和力结合C11/C12链脂肪酸的分子基础。ACDH-11螯合C11/C12链脂肪酸，并阻止这些脂肪酸激活核激素受体和驱动fat-7表达。因此，ACDH-11途径通过前所未有的脂肪酸信号传导模式将温度变化与脂质去饱和酶水平和膜流动性的调节联系起来，从而驱动热适应。
Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved C. elegans gene acdh-11 (acyl-CoA-dehydrogenase, ACDH) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat up-regulates acdh-11 expression to decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.
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DOI：
10.1073/pnas.90.16.7523
发表时间：
1993-08-15
影响因子：
11.1
作者：
KIM, JJP;WANG, M;PASCHKE, R
通讯作者：
PASCHKE, R
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
影响因子：
4.8
作者：
Dhe-Paganon, S;Duda, K;Shoelson, SE
通讯作者：
Shoelson, SE
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
McAndrew, Ryan P.;Wang, Yudong;Kim, Jung-Ja P.
通讯作者：
Kim, Jung-Ja P.