Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallès, Spain; Institut de Neurociències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain.
Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallès, Spain.
Prog Lipid Res. 2021 Jan;81:101071. doi: 10.1016/j.plipres.2020.101071. Epub 2020 Nov 10.
Nutrients, hormones and the energy sensor AMP-activated protein kinase (AMPK) tightly regulate the intracellular levels of the metabolic intermediary malonyl-CoA, which is a precursor of fatty acid synthesis and a negative regulator of fatty acid oxidation. In the brain, the involvement of malonyl-CoA in the control of food intake and energy homeostasis has been known for decades. However, recent data uncover a new role in cognition and brain development. The sensing of malonyl-CoA by carnitine palmitoyltransferase 1 (CPT1) proteins regulates a variety of functions, such as the fate of neuronal stem cell precursors, the motility of lysosomes in developing axons, the trafficking of glutamate receptors to the neuron surface (necessary for proper synaptic function) and the metabolic coupling between astrocytes and neurons. We discuss the relevance of those recent findings evidencing how nutrients and metabolic disorders impact cognition. We also enumerate all nutritional and hormonal conditions that are known to regulate malonyl-CoA levels in the brain, reflect on protein malonylation as a new post-translational modification, and give a reasoned vision of the opportunities and challenges that future research in the field could address.
营养素、激素和能量传感器 AMP 激活的蛋白激酶 (AMPK) 严格调控代谢中间产物丙二酰辅酶 A 的细胞内水平，丙二酰辅酶 A 是脂肪酸合成的前体和脂肪酸氧化的负调节剂。几十年来，人们已经知道丙二酰辅酶 A 在控制食物摄入和能量平衡方面的作用。然而，最近的数据揭示了它在认知和大脑发育中的新作用。肉毒碱棕榈酰基转移酶 1 (CPT1) 蛋白对丙二酰辅酶 A 的感知调节着各种功能，如神经元干细胞前体的命运、发育轴突中的溶酶体的运动、谷氨酸受体向神经元表面的运输（对于适当的突触功能是必需的）以及星形胶质细胞和神经元之间的代谢偶联。我们讨论了这些最近的发现的相关性，这些发现证明了营养物质和代谢紊乱如何影响认知。我们还列举了所有已知调节大脑中丙二酰辅酶 A 水平的营养和激素条件，思考蛋白质丙二酰化作为一种新的翻译后修饰，并对该领域未来研究可能解决的机会和挑战进行了合理的展望。
