Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver

IF 5.6 2区化学 Q1 CHEMISTRY, MEDICINAL

Journal of Chemical Information and Modeling Pub Date : 2024-04-25 DOI:10.1126/science.adk1005

Sinika Henschke, Hendrik Nolte, Judith Magoley, Tatjana Kleele, Claus Brandt, A. Christine Hausen, Claudia M. Wunderlich, Corinna A. Bauder, Philipp Aschauer, Suliana Manley, Thomas Langer, F. Thomas Wunderlich, Jens C. Brüning

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引用次数: 0

Abstract

Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in nutrient availability has remained unaddressed. Here, we found that sensory food perception rapidly induced mitochondrial fragmentation in the liver through protein kinase B/AKT (AKT)–dependent phosphorylation of serine 131 of the mitochondrial fission factor (MFFS131). This response was mediated by activation of hypothalamic pro-opiomelanocortin (POMC)–expressing neurons. A nonphosphorylatable MFF^S131G knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFF^S131G knock-in mice displayed altered liver mitochondrial dynamics and impaired insulin-stimulated suppression of hepatic glucose production. Thus, rapid activation of a hypothalamus–liver axis can adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism.

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食物感知促进肝脏中 MFFS131 的磷酸化和线粒体破碎

肝脏线粒体在适应不断变化的营养状态的新陈代谢过程中发挥着核心作用，但它们在营养供应预期变化时的动态调节问题仍未得到解决。在这里，我们发现感官食物知觉通过蛋白激酶 B/AKT (AKT)依赖的线粒体裂解因子（MFFS131）丝氨酸 131 磷酸化迅速诱导肝脏线粒体破碎。这种反应是通过激活下丘脑表达前绒毛膜促皮质素（POMC）的神经元介导的。在体外，非磷酸化的 MFFS131G 基因敲入突变会减弱 AKT 诱导的线粒体破碎。在体内，MFFS131G 基因敲入小鼠显示出肝脏线粒体动力学的改变，以及胰岛素刺激下抑制肝脏葡萄糖产生的功能受损。因此，快速激活下丘脑-肝脏轴可使线粒体功能适应预期的营养状态变化，从而控制肝脏葡萄糖代谢。

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来源期刊

Journal of Chemical Information and Modeling 化学-化学综合

CiteScore

9.80

自引率

10.70%

发文量

529

审稿时长

1.4 months

期刊介绍： The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery. Astute chemists, computer scientists, and information specialists look to this monthly’s insightful research studies, programming innovations, and software reviews to keep current with advances in this integral, multidisciplinary field. As a subscriber you’ll stay abreast of database search systems, use of graph theory in chemical problems, substructure search systems, pattern recognition and clustering, analysis of chemical and physical data, molecular modeling, graphics and natural language interfaces, bibliometric and citation analysis, and synthesis design and reactions databases.