SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in ob/ob mice.
SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in ob/ob mice.
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SIRT5 使代谢相关蛋白脱酰并减轻 ob/ob 小鼠的肝脂肪变性
DOI：
10.1016/j.ebiom.2018.09.037
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发表时间：
2018-10
期刊：
影响因子：
11.1
通讯作者：
Wei T
中科院分区：
文献类型：
--
作者：
Du Y;Hu H;Qu S;Wang J;Hua C;Zhang J;Wei P;He X;Hao J;Liu P;Yang F;Li T;Wei T
Sirtuin 5（SIRT 5）是一种NAD+依赖性赖氨酸脱酰酶。SIRT 5缺陷小鼠模型显示其在正常条件下代谢稳态是不稳定的。然而，SIRT 5和酰化在病理状态如肥胖和2型糖尿病（T2 D）中的生物学作用仍然难以捉摸。通过CRISPR/Cas9基因编辑工具建立肝脏SIRT 5过表达ob/ob小鼠模型（ob/ob-SIRT 5 OE），通过免疫沉淀偶联脂质色谱-串联质谱（LC-MS/MS）方法鉴定蛋白丙二酰化和琥珀酰化赖氨酸位点。ob/ob-SIRT 5 OE小鼠表现出丙二酰化和琥珀酰化降低，细胞糖酵解改善，脂肪生成抑制，脂肪酸氧化增强，肝脂肪变性减弱。对434个蛋白质上的955个丙二酰化位点和429个蛋白质上的1377个琥珀酰化位点进行了鉴定和定量。生物信息学分析表明，丙二酰化是糖酵解/糖异生途径中的主要SIRT 5靶标，而琥珀酰化是氧化磷酸化途径中的首选SIRT 5靶标。肝脏中SIRT 5的过表达改善了ob/ob小鼠的代谢异常，可能是通过主要代谢途径中的去丙二酸化和去琥珀酰化蛋白。SIRT 5及其相关的酰化可能是代谢紊乱的潜在靶点。国家重点研发计划、国家自然科学基金、中国科学院战略重点研究计划（A类）、北京大学跨学科医学种子基金、生物大分子国家实验室。
Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. The SIRT5 deficiency mouse model shows that it is dispensable for metabolic homeostasis under normal conditions. However, the biological role of SIRT5 and acylation in pathological states such as obesity and type 2 diabetes (T2D) remains elusive. The hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) was established by CRISPR/Cas9 gene editing tool Protein malonylation and succinylation lysine sites were identified by immunoprecipitation coupled lipid chromatography - tandem mass spectrometry (LC-MS/MS) methods. The ob/ob-SIRT5 OE mice showed decreased malonylation and succinylation, improved cellular glycolysis, suppressed gluconeogenesis, enhanced fatty acid oxidation, and attenuated hepatic steatosis. A total of 955 malonylation sites on 434 proteins and 1377 succinylation sites on 429 proteins were identified and quantitated. Bioinformatics analysis revealed that malonylation was the major SIRT5 target in the glycolysis/gluconeogenesis pathway, whereas succinylation was the preferred SIRT5 target in the oxidative phosphorylation pathway. Hepatic overexpression of SIRT5 ameliorated the metabolic abnormalities of ob/ob mice, probably through demalonylating and desuccinylating proteins in the main metabolic pathways. SIRT5 and related acylation might be potential targets for metabolic disorders. National Key R&D Program of China, the National Natural Science Foundation of China, the Strategic Priority Research Programs (Category A) of the Chinese Academy of Sciences, the Interdisciplinary Medicine Seed Fund of Peking University and the National Laboratory of Biomacromolecules.
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影响因子：
16
作者：
Nishida Y;Rardin MJ;Carrico C;He W;Sahu AK;Gut P;Najjar R;Fitch M;Hellerstein M;Gibson BW;Verdin E
通讯作者：
Verdin E
DOI：
10.1093/bioinformatics/bts251
发表时间：
2012-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jiao X;Sherman BT;Huang da W;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
赖氨酸丙二酰化的蛋白质组学和生化研究表明其在线粒体功能和脂肪酸氧化中与丙二酸尿症相关的调节作用。
影响因子：
7
作者：
Colak, Gozde;Pougovkina, Olga;Zhao, Yingming
通讯作者：
Zhao, Yingming
影响因子：
4.8
作者：
Liszt, G;Ford, E;Guarente, L
通讯作者：
Guarente, L
影响因子：
4.8
作者：
Hershberger, Kathleen A.;Abraham, Dennis M.;Hirschey, Matthew D.
通讯作者：
Hirschey, Matthew D.