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一种有前景的针对 ERMMDs 的抗肿瘤靶向治疗方法,通过靶向作用于肿瘤细胞内异常的脂质代谢。

A promising anti-tumor targeting on ERMMDs mediated abnormal lipid metabolism in tumor cells.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Cell Death Dis. 2024 Aug 4;15(8):562. doi: 10.1038/s41419-024-06956-4.

Abstract

The investigation of aberrations in lipid metabolism within tumor has become a burgeoning field of study that has garnered significant attention in recent years. Lipids can serve as a potent source of highly energetic fuel to support the rapid growth of neoplasia, in where the ER-mitochondrial membrane domains (ERMMDs) provide an interactive network for facilitating communication between ER and mitochondria as well as their intermembrane space and adjunctive proteins. In this review, we discuss fatty acids (FAs) anabolic and catabolic metabolism, as well as how CPT1A-VDAC-ACSL clusters on ERMMDs participate in FAs transport, with a major focus on ERMMDs mediated collaborative loop of FAO, Ca transmission in TCA cycle and OXPHOS process. Here, we present a comprehensive perspective on the regulation of aberrant lipid metabolism through ERMMDs conducted tumor physiology might be a promising and potential target for tumor starvation therapy.

摘要

肿瘤内脂质代谢异常的研究已经成为一个新兴的研究领域,近年来受到了广泛关注。脂质可以作为一种高能燃料的来源,为肿瘤的快速生长提供支持,内质网-线粒体膜结构域(ERMMDs)为内质网和线粒体之间以及它们的膜间隙和附属蛋白之间的交流提供了一个相互作用的网络。在这篇综述中,我们讨论了脂肪酸(FAs)的合成和分解代谢,以及 ERMMDs 上的 CPT1A-VDAC-ACSL 簇如何参与 FAs 的转运,重点是 ERMMDs 介导的 FAO、TCA 循环中的 Ca 传递和 OXPHOS 过程的协同循环。在这里,我们提出了一个全面的观点,即通过 ERMMDs 进行肿瘤生理学调节异常脂质代谢可能是肿瘤饥饿治疗的一个有前途和潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c88/11298533/ca18eaa190c4/41419_2024_6956_Fig1_HTML.jpg

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