Functional mitochondrial respiration is essential for glioblastoma tumour growth.

IF 6.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2025-05-05 DOI:10.1038/s41388-025-03429-6

Petra Brisudova, Dana Stojanovic, Jaromir Novak, Zuzana Nahacka, Gabriela Lopes Oliveira, Ondrej Vanatko, Sarka Dvorakova, Berwini Endaya, Jaroslav Truksa, Monika Kubiskova, Alice Foltynova, Daniel Jirak, Natalia Jirat-Ziolkowska, Lukas Kucera, Karel Chalupsky, Krystof Klima, Jan Prochazka, Radislav Sedlacek, Francesco Mengarelli, Patrick Orlando, Luca Tiano, Paulo J Oliveira, Carole Grasso, Michael V Berridge, Renata Zobalova, Miroslava Anderova, Jiri Neuzil

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Abstract

Horizontal transfer of mitochondria from the tumour microenvironment to cancer cells to support proliferation and enhance tumour progression has been shown for various types of cancer in recent years. Glioblastoma, the most aggressive adult brain tumour, has proven to be no exception when it comes to dynamic intercellular mitochondrial movement, as shown in this study using an orthotopic tumour model of respiration-deficient glioblastoma cells. Although confirmed mitochondrial transfer was shown to facilitate tumour progression in glioblastoma, we decided to investigate whether the related electron transport chain recovery is necessary for tumour formation in the brain. Based on experiments using time-resolved analysis of tumour formation by glioblastoma cells depleted of their mitochondrial DNA, we conclude that functional mitochondrial respiration is essential for glioblastoma growth in vivo, because it is needed to support coenzyme Q redox cycling for de novo pyrimidine biosynthesis controlled by respiration-linked dihydroorotate dehydrogenase enzyme activity. We also demonstrate here that astrocytes are key mitochondrial donors in this model.

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功能性线粒体呼吸对胶质母细胞瘤的生长至关重要。

近年来，线粒体从肿瘤微环境向癌细胞的水平转移以支持增殖和促进肿瘤进展已被证明适用于各种类型的癌症。胶质母细胞瘤是最具侵袭性的成人脑肿瘤，当涉及到动态的细胞间线粒体运动时，也不例外，正如本研究使用呼吸缺陷胶质母细胞瘤细胞的原位肿瘤模型所示。虽然证实线粒体转移可促进胶质母细胞瘤的肿瘤进展，但我们决定研究相关的电子传递链恢复是否对脑内肿瘤形成是必要的。基于对线粒体DNA缺失的胶质母细胞瘤细胞形成肿瘤的时间分辨率分析，我们得出结论，线粒体呼吸功能对胶质母细胞瘤的体内生长至关重要，因为它需要支持辅酶Q氧化还原循环，以进行由呼吸连接的二氢羟酸脱氢酶活性控制的新生嘧啶生物合成。我们在这里也证明了星形胶质细胞是这个模型中关键的线粒体供体。

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

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.