Functional mitochondrial respiration is essential for glioblastoma tumour growth
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.
Authors
- Zuzana Nahácka (ORCID: https://orcid.org/0000-0003-0477-2764)
- Michael V. Berridge (ORCID: https://orcid.org/0000-0003-2619-7473)
- Lukáš Kučera (ORCID: https://orcid.org/0000-0002-0009-5105)
- Karel Chalupský (ORCID: https://orcid.org/0000-0001-6890-6464)
- Ondřej Vaňátko (ORCID: https://orcid.org/0000-0001-5800-6358)
- Jaromı́r Novák (ORCID: https://orcid.org/0000-0001-5851-9399)
- Miroslava Anděrová (ORCID: https://orcid.org/0000-0002-9030-4571)
- Monika Kubiskova
- Berwini Endaya (ORCID: https://orcid.org/0000-0002-4072-4332)
- Jaroslav Truksa (ORCID: https://orcid.org/0000-0002-8967-7354)
- Radislav Sedláček (ORCID: https://orcid.org/0000-0002-3352-392X)
- Carole Grasso (ORCID: https://orcid.org/0000-0002-0162-5139)
- Daniel Jirák (ORCID: https://orcid.org/0000-0001-6834-3462)
- Petra Brisudová (ORCID: https://orcid.org/0009-0001-9751-9356)
- Kryštof Klíma (ORCID: https://orcid.org/0009-0006-3374-9060)
- Jiřı́ Neužil (ORCID: https://orcid.org/0000-0002-2478-2460)
- Gabriela Lopes Oliveira (ORCID: https://orcid.org/0000-0001-5258-3322)
- Sarka Dvorakova
- Dražen Stojanović (ORCID: https://orcid.org/0000-0002-4028-9342)
- Luca Tiano (ORCID: https://orcid.org/0000-0002-7519-7106)
- Renata Zobalová (ORCID: https://orcid.org/0000-0002-9097-4700)
- Francesco Mengarelli (ORCID: https://orcid.org/0009-0002-1229-5443)
- Paulo J. Oliveira (ORCID: https://orcid.org/0000-0002-5201-9948)
- Patrick Orlando (ORCID: https://orcid.org/0000-0002-7103-4967)
- Jan Procházka
- Alice Foltynova
- Natalia Jirat-Ziolkowska
Institutions
- Griffith University (AU)
- Marche Polytechnic University (IT)
- Malaghan Institute of Medical Research (NZ)
- Czech Academy of Sciences (CZ)
- Charles University (CZ)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Institute of Clinical and Experimental Medicine (CZ)
- Czech Academy of Sciences, Institute of Experimental Medicine (CZ)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- University of Coimbra (PT)
Publication Details
- Journal
- Oncogene
- Published
- 2025-05-05
- DOI
- https://doi.org/10.1038/s41388-025-03429-6
- Citations
- 13
- Primary Topic
- ATP Synthase and ATPases Research
- Type
- article
- Field-Weighted Citation Impact
- 10.48
Funders
- Univerzita Karlova v Praze
- Grantová Agentura, Univerzita Karlova
- Grantová Agentura České Republiky
- Ministerstvo Zdravotnictví Ceské Republiky
- Agentura Pro Zdravotnický Výzkum České Republiky