Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue.
Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue.
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DOI：
10.1016/j.jmb.2020.09.022
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发表时间：
2020-11-20
影响因子：
5.6
通讯作者：
Shewchuk BM
中科院分区：
文献类型：
--
作者：
Patel BV;Yao F;Howenstine A;Takenaka R;Hyatt JA;Sears KE;Shewchuk BM
线粒体脂肪酸氧化（FAO）有助于在许多哺乳动物组织中驱动ATP合成的质子动力。在真动物（胎盘）哺乳动物中，棕色脂肪组织（BAT）也可以通过解偶联蛋白1 （UCP1）消散质子梯度以产生热量，但BAT出现背后的进化事件尚不清楚。粮农组织的一个重要步骤是将细胞质长链酰基辅酶A（酰基辅酶A）转运到线粒体基质中，这需要横纹肌和BAT中的肉毒碱棕榈酰基转移酶1B （CPT1B）的作用。在真动物中，CPT1B基因与胆碱激酶β (CHKB)基因紧密相连，CHKB基因是从同一条DNA链转录而来，终止于CPT1B的上游。CHKB是合成磷脂酰胆碱（PC）的限速酶，PC是一种主要的线粒体膜磷脂，这表明CHKB和CPT1B的协同表达可能共同增强线粒体FAO。目前的研究结果表明，真动物CHKB和CPT1B基因的转录在一个针对CHKB基因的单一表观遗传域内连接，并且这种调控联系似乎是由真动物基因间缺失导致的，该缺失显著改变了CHKB和CPT1B的表达分布。根据这一事件与BAT出现的时间、CHKB-CPT1B的系统发育以及UCP1的不足来解释真兽BAT，这些数据支持了BAT出现的机制，该机制基于在现有UCP1的背景下获得脂肪细胞FAO的新能力。
Mitochondrial fatty acid oxidation (FAO) contributes to the proton motive force that drives ATP synthesis in many mammalian tissues. In eutherian (placental) mammals, brown adipose tissue (BAT) can also dissipate this proton gradient through uncoupling protein 1 (UCP1) to generate heat, but the evolutionary events underlying the emergence of BAT are unknown. An essential step in FAO is the transport of cytoplasmic long-chain acyl-coenzyme A (acyl-CoA) into the mitochondrial matrix, which requires the action of carnitine palmitoyltransferase 1B (CPT1B) in striated muscle and BAT. In eutherians, the CPT1B gene is closely linked to the choline kinase beta (CHKB) gene, which is transcribed from the same DNA strand and terminates just upstream of CPT1B. CHKB is a rate-limiting enzyme in the synthesis of phosphatidylcholine (PC), a predominant mitochondrial membrane phospholipid, suggesting that the coordinated expression of CHKB and CPT1B may cooperatively enhance mitochondrial FAO. The present findings show that transcription of the eutherian CHKB and CPT1B genes is linked within a unitary epigenetic domain targeted to the CHKB gene, and that that this regulatory linkage appears to have resulted from an intergenic deletion in eutherians that significantly altered the distribution of CHKB and CPT1B expression. Informed by the timing of this event relative to the emergence of BAT, the phylogeny of CHKB-CPT1B synteny, and the insufficiency of UCP1 to account for eutherian BAT, these data support a mechanism for the emergence of BAT based on the acquisition of a novel capacity for adipocyte FAO in a background of extant UCP1.
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影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
29
作者：
Harms MJ;Ishibashi J;Wang W;Lim HW;Goyama S;Sato T;Kurokawa M;Won KJ;Seale P
通讯作者：
Seale P
影响因子：
10.5
作者：
Berger, Shelley L.;Kouzarides, Tony;Shilatifard, Ali
通讯作者：
Shilatifard, Ali
影响因子：
3.3
作者：
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通讯作者：
Spiegelman BM
影响因子：
3.6
作者：
Auinger, A.;Rubin, D.;Schrezenmeir, J.
通讯作者：
Schrezenmeir, J.