少突胶质前体细胞特异性阻断低糖诱导的AMPK激活，确保髓鞘形成和再髓鞘形成。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-10-22 DOI:10.1038/s42255-025-01386-8

Yuxia Sun,Wei-Wei Zhang,Lu Men,Jianfeng Wu,Luming Yao,Xi Huang,Yaying Wu,Cixiong Zhang,Ying Chen,David Carling,Chen-Song Zhang,Sheng-Cai Lin

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引用次数: 0

摘要

研究表明，在大多数细胞中，低糖通过溶酶体葡萄糖感应途径导致amp激活的蛋白激酶（AMPK）的激活，其中糖酵解醛缩酶作为葡萄糖传感器。在这里，我们发现ALDOC（醛缩酶C）是小鼠和大鼠少突胶质前体细胞（OPCs）中醛缩酶的主要同工酶，在赖氨酸14位点乙酰化，使溶酶体葡萄糖感应AMPK途径无法运作。我们发现，阻断AMPK激活是OPCs正常增殖和分化为成熟少突胶质细胞的必要条件，在发育过程中形成髓鞘，在局部葡萄糖水平低的脱髓鞘区域重新形成髓鞘。因此，醛缩酶的乙酰化作为AMPK在低糖反应中激活的一个检查点，以确保OPCs在髓鞘形成和脱髓鞘神经元的再髓鞘形成中的增殖和分化。

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Oligodendrocyte precursor cell-specific blocking of low-glucose-induced activation of AMPK ensures myelination and remyelination.

It has been shown that in most cells, low glucose leads to activation of AMP-activated protein kinase (AMPK) via the lysosomal glucose-sensing pathway, where glycolytic aldolase acts as the glucose sensor. Here, we show that ALDOC (aldolase C), the predominant isozyme of aldolase in mouse and rat oligodendrocyte precursor cells (OPCs), is acetylated at lysine 14, making the lysosomal glucose-sensing AMPK pathway unable to operate. We find that the blockage of AMPK activation is required for the proper proliferation and differentiation of OPCs into mature oligodendrocytes for myelination during development and for remyelination in areas of demyelination where the local glucose levels are low. Therefore, the acetylation of aldolase acts as a checkpoint for AMPK activation in response to low glucose to ensure the proliferation and differentiation of OPCs for myelination, and remyelination of demyelinated neurons.

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.