Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation
文献类型:期刊论文
作者 | Colak, Gozde2; Pougovkina, Olga3; Dai, Lunzhi2; Tan, Minjia5![]() |
刊名 | MOLECULAR & CELLULAR PROTEOMICS
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出版日期 | 2015-11 |
卷号 | 14期号:11页码:3056-3071 |
ISSN号 | 1535-9476 |
DOI | 10.1074/mcp.M115.048850 |
文献子类 | Article |
英文摘要 | The protein substrates of sirtuin 5-regulated lysine malonylation (Kmal) remain unknown, hindering its functional analysis. In this study, we carried out proteomic screening, which identified 4042 Kmal sites on 1426 proteins in mouse liver and 4943 Kmal sites on 1822 proteins in human fibroblasts. Increased malonyl-CoA levels in malonyl-CoA decarboxylase (MCD)-deficient cells induces Kmal levels in substrate proteins. We identified 461 Kmal sites showing more than a 2-fold increase in response to MCD deficiency as well as 1452 Kmal sites detected only in MCD-/- fibroblast but not MCD+/+ cells, suggesting a pathogenic role of Kmal in MCD deficiency. Cells with increased lysine malonylation displayed impaired mitochondrial function and fatty acid oxidation, suggesting that lysine malonylation plays a role in pathophysiology of malonic aciduria. Our study establishes an association between Kmal and a genetic disease and offers a rich resource for elucidating the contribution of the Kmal pathway and malonyl-CoA to cellular physiology and human diseases. |
WOS关键词 | COA DECARBOXYLASE DEFICIENCY ; COENZYME-A ; POSTTRANSLATIONAL MODIFICATION ; BETA-OXIDATION ; COMPLEX-I ; ACETYLATION ; IDENTIFICATION ; SUCCINYLATION ; SIRT5 ; PHOSPHORYLATION |
资助项目 | Telethon Italy[GTB12001] |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000365636800017 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
源URL | [http://119.78.100.183/handle/2S10ELR8/276340] ![]() |
专题 | 化学蛋白质组学研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | de Boer, Vincent C. J. |
作者单位 | 1.Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA; 2.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA; 3.Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, Emmas Children Hosp,Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands; 4.Univ Amsterdam, Acad Med Ctr, Dept Pediat, Emmas Children Hosp, NL-1105 AZ Amsterdam, Netherlands; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 6.PTM Biolabs, Chicago, IL 60612 USA; 7.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA; 8.Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA; 9.Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England |
推荐引用方式 GB/T 7714 | Colak, Gozde,Pougovkina, Olga,Dai, Lunzhi,et al. Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation[J]. MOLECULAR & CELLULAR PROTEOMICS,2015,14(11):3056-3071. |
APA | Colak, Gozde.,Pougovkina, Olga.,Dai, Lunzhi.,Tan, Minjia.,te Brinke, Heleen.,...&Zhao, Yingming.(2015).Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation.MOLECULAR & CELLULAR PROTEOMICS,14(11),3056-3071. |
MLA | Colak, Gozde,et al."Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation".MOLECULAR & CELLULAR PROTEOMICS 14.11(2015):3056-3071. |
入库方式: OAI收割
来源:上海药物研究所
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