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.

Biomedical Research Center University Hospital Hradec Kralove Czech Republic

Danish Cancer Society Research Center Copenhagen Denmark

Division of Genome Biology Department of Medical Biochemistry and Biophysics Science for Life Laboratory Karolinska Institute Stockholm Sweden

Laboratory of Bioenergetics Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Genome Integrity Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

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