MICU2 up-regulation enhances tumor aggressiveness and metabolic reprogramming during colorectal cancer development.

IF 9.8 1区生物学 Q1 Agricultural and Biological Sciences PLoS Biology Pub Date : 2024-10-28 eCollection Date: 2024-10-01 DOI:10.1371/journal.pbio.3002854

Alison Robert, David Crottès, Jérôme Bourgeais, Naig Gueguen, Arnaud Chevrollier, Jean-François Dumas, Stéphane Servais, Isabelle Domingo, Stéphanie Chadet, Julien Sobilo, Olivier Hérault, Thierry Lecomte, Christophe Vandier, William Raoul, Maxime Guéguinou

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Abstract

The mitochondrial Ca2+ uniporter (MCU) plays crucial role in intramitochondrial Ca2+ uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated. Here, we describe the role of MICU2 in cell proliferation and invasion using in vitro and in vivo models of human colorectal cancer (CRC). Transcriptomic analysis demonstrated an increase in MICU2 expression and the MICU2/MICU1 ratio in advanced CRC and CRC-derived metastases. We report that expression of MICU2 is necessary for mitochondrial Ca2+ uptake and quality of the mitochondrial network. Our data reveal the interplay between MICU2 and MICU1 in the metabolic flexibility between anaerobic glycolysis and OXPHOS. Overall, our study sheds light on the potential role of the MICUs in diseases associated with metabolic reprogramming.

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MICU2 的上调增强了结直肠癌发展过程中的肿瘤侵袭性和代谢重编程。

线粒体 Ca2+ 单端口（MCU）在线粒体内 Ca2+ 摄取中发挥着关键作用，使 Ca2+ 依赖性激活氧化代谢。近几十年来，MCU 孔形成蛋白在癌症中的作用一直备受关注。然而，与 MCU 相关的调控蛋白线粒体钙摄取 1 和 2（MICU1 和 MICU2）对病理生理状况的贡献却鲜有研究。在此，我们利用体外和体内人类结直肠癌（CRC）模型描述了 MICU2 在细胞增殖和侵袭中的作用。转录组分析表明，在晚期 CRC 和 CRC 衍生的转移灶中，MICU2 的表达和 MICU2/MICU1 的比例都有所增加。我们报告说，MICU2 的表达是线粒体 Ca2+ 摄取和线粒体网络质量所必需的。我们的数据揭示了 MICU2 和 MICU1 在无氧糖酵解和 OXPHOS 之间的代谢灵活性中的相互作用。总之，我们的研究揭示了 MICU 在代谢重编程相关疾病中的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY

CiteScore

15.40

自引率

2.00%

发文量

359

审稿时长

3-8 weeks

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