Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase.
Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase.
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衣康酸通过抑制线粒体复合体II和甲基丙二酰辅酶A变位酶来改变琥珀酸和辅酶A的代谢。
DOI：
10.3390/metabo11020117
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发表时间：
2021-02-18
期刊：
影响因子：
4.1
通讯作者：
Metallo CM
中科院分区：
文献类型：
--
作者：
Cordes T;Metallo CM
衣康酸是一种小分子代谢物，由哺乳动物细胞中顺乌头酸脱羧酶-1（ACOD1）内源性产生，影响许多细胞过程。衣康酸在细胞中的代谢结果是多样的，并有助于其调节功能。在这里，我们应用同位素示踪和质谱方法来探索衣康酸盐如何影响培养细胞中的各种代谢途径。衣康酸是复合物II/琥珀酸脱氢酶（SDH）的竞争性和可逆性抑制剂，其改变三羧酸（TCA）循环代谢，导致琥珀酸积累。在用辅酶A（CoA）活化后，衣康酰辅酶A抑制腺苷钴胺素介导的甲基丙二酰辅酶A（MUT）活性，从而间接影响支链氨基酸（BCAA）代谢和脂肪酸多样性。因此，衣康酸通过其对TCA、氨基酸、维生素B12和CoA代谢的影响来改变线粒体中CoA种类的平衡。我们的研究结果强调了衣康酸调节的多种代谢途径，并提供了一个路线图，将这些代谢产物与潜在的下游生物功能联系起来。
Itaconate is a small molecule metabolite that is endogenously produced by cis-aconitate decarboxylase-1 (ACOD1) in mammalian cells and influences numerous cellular processes. The metabolic consequences of itaconate in cells are diverse and contribute to its regulatory function. Here, we have applied isotope tracing and mass spectrometry approaches to explore how itaconate impacts various metabolic pathways in cultured cells. Itaconate is a competitive and reversible inhibitor of Complex II/succinate dehydrogenase (SDH) that alters tricarboxylic acid (TCA) cycle metabolism leading to succinate accumulation. Upon activation with coenzyme A (CoA), itaconyl-CoA inhibits adenosylcobalamin-mediated methylmalonyl-CoA (MUT) activity and, thus, indirectly impacts branched-chain amino acid (BCAA) metabolism and fatty acid diversity. Itaconate, therefore, alters the balance of CoA species in mitochondria through its impacts on TCA, amino acid, vitamin B12, and CoA metabolism. Our results highlight the diverse metabolic pathways regulated by itaconate and provide a roadmap to link these metabolites to potential downstream biological functions.
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Itaconate连接琥珀酸脱氢酶与巨噬细胞代谢重塑和调节炎症的联系。
影响因子：
29
作者：
Lampropoulou V;Sergushichev A;Bambouskova M;Nair S;Vincent EE;Loginicheva E;Cervantes-Barragan L;Ma X;Huang SC;Griss T;Weinheimer CJ;Khader S;Randolph GJ;Pearce EJ;Jones RG;Diwan A;Diamond MS;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
29
作者：
Divakaruni AS;Hsieh WY;Minarrieta L;Duong TN;Kim KKO;Desousa BR;Andreyev AY;Bowman CE;Caradonna K;Dranka BP;Ferrick DA;Liesa M;Stiles L;Rogers GW;Braas D;Ciaraldi TP;Wolfgang MJ;Sparwasser T;Berod L;Bensinger SJ;Murphy AN
通讯作者：
Murphy AN
DOI：
10.1007/978-1-4939-9236-2_14
发表时间：
2019-01-01
期刊：
HIGH-THROUGHPUT METABOLOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Cordes, Thekla;Metallo, Christian M.
通讯作者：
Metallo, Christian M.
影响因子：
64.5
作者：
Dang EV;Barbi J;Yang HY;Jinasena D;Yu H;Zheng Y;Bordman Z;Fu J;Kim Y;Yen HR;Luo W;Zeller K;Shimoda L;Topalian SL;Semenza GL;Dang CV;Pardoll DM;Pan F
通讯作者：
Pan F
影响因子：
64.8
作者：
Bambouskova M;Gorvel L;Lampropoulou V;Sergushichev A;Loginicheva E;Johnson K;Korenfeld D;Mathyer ME;Kim H;Huang LH;Duncan D;Bregman H;Keskin A;Santeford A;Apte RS;Sehgal R;Johnson B;Amarasinghe GK;Soares MP;Satoh T;Akira S;Hai T;de Guzman Strong C;Auclair K;Roddy TP;Biller SA;Jovanovic M;Klechevsky E;Stewart KM;Randolph GJ;Artyomov MN
通讯作者：
Artyomov MN