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核内三羧酸循环与线粒体过载:肿瘤代谢的新萌芽

Intranuclear TCA and mitochondrial overload: The nascent sprout of tumors metabolism.

作者信息

Yuan Weixi, Lu Guozhong, Zhao Yin, He Xiang, Liao Senyi, Wang Zhe, Lei Xiaoyong, Xie Zhizhong, Yang Xiaoyan, Tang Shengsong, Tang Guotao, Deng Xiangping

机构信息

The First Affiliated Hospital, Department of Pharmacy, Institute of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.

922nd Hospital of Hengyang, 421001, Hunan, China.

出版信息

Cancer Lett. 2025 Mar 31;613:217527. doi: 10.1016/j.canlet.2025.217527. Epub 2025 Feb 3.

Abstract

Abnormal glucose metabolism in tumors is a well-known form of metabolic reprogramming in tumor cells, the most representative of which, the Warburg effect, has been widely studied and discussed since its discovery. However, contradictions in a large number of studies and suboptimal efficacy of drugs targeting glycolysis have prompted us to further deepen our understanding of glucose metabolism in tumors. Here, we review recent studies on mitochondrial overload, nuclear localization of metabolizing enzymes, and intranuclear TCA (nTCA) in the context of the anomalies produced by inhibition of the Warburg effect. We provide plausible explanations for many of the contradictory points in the existing studies, including the causes of the Warburg effect. Furthermore, we provide a detailed prospective discussion of these studies in the context of these new findings, providing new ideas for the use of nTCA and mitochondrial overload in tumor therapy.

摘要

肿瘤中的异常葡萄糖代谢是肿瘤细胞中一种广为人知的代谢重编程形式,其中最具代表性的瓦伯格效应自发现以来就受到了广泛的研究和讨论。然而,大量研究中的矛盾以及靶向糖酵解药物的疗效欠佳促使我们进一步加深对肿瘤中葡萄糖代谢的理解。在此,我们在抑制瓦伯格效应所产生的异常情况背景下,综述了近期关于线粒体过载、代谢酶的核定位以及核内三羧酸循环(nTCA)的研究。我们对现有研究中的许多矛盾点,包括瓦伯格效应的成因,给出了合理的解释。此外,我们在这些新发现的背景下对这些研究进行了详细的前瞻性讨论,为在肿瘤治疗中利用nTCA和线粒体过载提供了新思路。

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