The silencing of adenine nucleotide translocase isoform 1 induces oxidative stress and programmed cell death in ADF human glioblastoma cells.
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.
Dipartimento di Morfologia Umana e Biologia Applicata, University of Pisa, Pisa, Italy.
Annalisa
A
Lena
Mariarosa
M
Rechichi
Alessandra
A
Salvetti
Donatella
D
Vecchio
Monica
M
Evangelista
Giuseppe
G
Rainaldi
Vittorio
V
Gremigni
Leonardo
L
Rossi
D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D020868:Gene Silencing; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress; D014407:Tumor Cells, Cultured
D033741:Adenine Nucleotide Translocator 1