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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引用次数: 0

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.

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。
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来源期刊
PLoS Biology
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
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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