Mitochondrial phosphatidylethanolamine modulates UCP1 to promote brown adipose thermogenesis.
Mitochondrial phosphatidylethanolamine modulates UCP1 to promote brown adipose thermogenesis.
复制标题
DOI：
10.1126/sciadv.ade7864
复制
发表时间：
2023-02-24
期刊：
影响因子：
13.6
通讯作者：
Funai K
中科院分区：
文献类型：
--
作者：
Johnson JM;Peterlin AD;Balderas E;Sustarsic EG;Maschek JA;Lang MJ;Jara-Ramos A;Panic V;Morgan JT;Villanueva CJ;Sanchez A;Rutter J;Lodhi IJ;Cox JE;Fisher-Wellman KH;Chaudhuri D;Gerhart-Hines Z;Funai K
解偶联蛋白1 （UCP1）产热是棕色脂肪组织（BAT）增加能量消耗的主要机制之一。UCP1位于线粒体内膜（IMM），在那里它独立于三磷酸腺苷（ATP）合成酶消散膜电位。在这里，我们提供的证据表明，磷脂酰乙醇胺（PE）通过IMM调节ucp1依赖的质子电导来调节产热。线粒体脂质组学分析显示PE是一个特征分子，其丰度与产热负荷的变化有双向反应。通过删除磷脂酰丝氨酸脱羧酶（PSD）减少线粒体PE，使小鼠对寒冷不耐受，对β3肾上腺素能受体激动剂诱导的全身耗氧量增加不敏感。BAT线粒体的高分辨率呼吸测定和荧光测定显示，线粒体PE的丧失特异性地降低了ucp1依赖的呼吸，而不影响电子传递效率或ATP合成。这些发现被pe缺陷有丝分裂体中UCP1质子电流的减少所证实。因此，PE作为一种温度响应变阻器，调节ucp1依赖性产热，发挥了以前未知的作用。磷脂酰乙醇胺通过调节UCP1活性，在棕色脂肪产热过程中发挥了以前未知的作用。
Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist–induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis. Phosphatidylethanolamine performs a previously unknown role in brown adipose thermogenesis by modulating UCP1 activity.
登录
查看更多内容
DOI：
10.1016/j.tem.2016.05.007
发表时间：
2016-08
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Heden TD;Neufer PD;Funai K
通讯作者：
Funai K
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
影响因子：
2.8
作者：
Chung, Dillon J.;Sparagna, Genevieve C.;Schulte, Patricia M.
通讯作者：
Schulte, Patricia M.
影响因子：
4.4
作者：
BARTH, PG;SCHOLTE, HR;SOBOTKAPLOJHAR, MA
通讯作者：
SOBOTKAPLOJHAR, MA
影响因子：
7.4
作者：
Jovanovic O;Pashkovskaya AA;Annibal A;Vazdar M;Burchardt N;Sansone A;Gille L;Fedorova M;Ferreri C;Pohl EE
通讯作者：
Pohl EE