Determination of <scp>ADP</scp>/<scp>ATP</scp> translocase isoform ratios in malignancy and cellular senescence
Cellular senescence has recently been recognized as a significant contributor to the poor prognosis of glioblastoma, one of the most aggressive brain tumors. Consequently, effectively eliminating senescent glioblastoma cells could benefit patients. Human ADP/ATP translocases (ANTs) play a role in oxidative phosphorylation in both normal and tumor cells. Previous research has shown that the sensitivity of senescent cells to mitochondria-targeted senolytics depends on the level of ANT2. Here, we systematically mapped the transcript and protein levels of ANT isoforms in various types of senescence and glioblastoma tumorigenesis. We employed bioinformatics analysis, targeted mass spectrometry, RT-PCR, immunoblotting, and assessment of cellular energy state to elucidate how individual ANT isoforms are expressed during the development of senescence in noncancerous and glioblastoma cells. We observed a consistent elevation of ANT1 protein levels across all tested senescence types, while ANT2 and ANT3 exhibited variable changes. Alterations in ANT protein isoform levels correlated with shifts in the cellular oxygen consumption rate. Our findings suggest that ANT isoforms are mutually interchangeable for oxidative phosphorylation and manipulating individual ANT isoforms could have potential for senolytic therapy.
Authors
- Vojtěch Tambor (ORCID: https://orcid.org/0000-0001-7872-7443)
- Tomáš Mráček (ORCID: https://orcid.org/0000-0002-9492-0718)
- Zdeněk Hodný (ORCID: https://orcid.org/0000-0002-6454-6796)
- Zuzana Liblova
- Josef Novák (ORCID: https://orcid.org/0000-0002-9764-6195)
- Ivo Fabrik (ORCID: https://orcid.org/0000-0002-3027-1253)
- Rudolf Kupčík (ORCID: https://orcid.org/0000-0002-4199-6321)
- Martha T. Kratky
- Alena Pecinová (ORCID: https://orcid.org/0000-0002-0204-7502)
- David Rysanek (ORCID: https://orcid.org/0000-0002-5131-0055)
- Pinky Sultana (ORCID: https://orcid.org/0000-0002-5744-9023)
- Barbora Šalovská (ORCID: https://orcid.org/0000-0002-7093-4576)
- Marie Vajrychová (ORCID: https://orcid.org/0000-0002-9495-8046)
- Pavla Vašicová (ORCID: https://orcid.org/0000-0002-9733-9929)
- Ladislav Anděra (ORCID: https://orcid.org/0000-0003-3073-2280)
- Zuzana Korandová (ORCID: https://orcid.org/0000-0001-8143-3681)
- Jiří Bártek (ORCID: https://orcid.org/0000-0003-2013-7525)
- Dominika Maurencova
- Pavel Kashmel
Institutions
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- University Hospital Hradec Králové (CZ)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Danish Cancer Society (DK)
- Czech Academy of Sciences, Institute of Physiology (CZ)
Publication Details
- Journal
- Molecular Oncology
- Published
- 2025-04-27
- DOI
- https://doi.org/10.1002/1878-0261.70039
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Health
- Danish Cancer Society Research Center
- Grantová Agentura České Republiky
- Danmarks Frie Forskningsfond