Journal
FEBS JOURNAL
Volume 277, Issue 13, Pages 2853-2867Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1742-4658.2010.07702.x
Keywords
adenine nucleotide translocase; ADF cells; glioblastoma multiforme; mitochondrion; reactive oxygen species
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Funding
- Fondi per il finanziamento progetti di ricerca Istituto Toscano Tumori (ITT)
- Fondazione Cassa di Risparmio di Livorno
- Fondazione Cassa di Risparmio di Lucca, Italy
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Adenine nucleotide translocases (ANTs) are multitask proteins involved in several aspects of cell metabolism, as well as in the regulation of cell death/survival processes. We investigated the role played by ANT isoforms 1 and 2 in the growth of a human glioblastoma cell line (ADF cells). The silencing of ANT2 isoform, by small interfering RNA, did not produce significant changes in ADF cell viability. By contrast, the silencing of ANT1 isoform strongly reduced ADF cell viability by inducing a non-apoptotic cell death process resembling paraptosis. We demonstrated that cell death induced by ANT1 depletion cannot be ascribed to the loss of the ATP/ADP exchange function of this protein. By contrast, our findings indicate that ANT1-silenced cells experience oxidative stress, thus allowing us to hypothesize that the effect of ANT1-silencing on ADF is mediated by the loss of the ANT1 uncoupling function. Several studies ascribe a pro-apoptotic role to ANT1 as a result of the observation that ANT1 overexpression sensitizes cells to mitochondrial depolarization or to apoptotic stimuli. In the present study, we demonstrate that, despite its pro-apoptotic function at a high expression level, the reduction of ANT1 density below a physiological baseline impairs fundamental functions of this protein in ADF cells, leading them to undertake a cell death process.
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