Changes in the expression of the human adenine nucleotide translocase isoforms condition cellular metabolic/proliferative status.

Human cells express four mitochondrial adenine nucleotide translocase (hANT) isoforms that are tissue-specific and developmentally regulated. hANT1 is mainly expressed in terminally differentiated muscle cells; hANT2 is growth-regulated and is upregulated in highly glycolytic and proliferative cells; and hANT3 is considered to be ubiquitous and non-specifically regulated. Here, we studied how the expression of hANT isoforms is regulated by proliferation and in response to metabolic stimuli, and examined the metabolic consequences of their silencing and overexpression.

Expression of human and mouse adenine nucleotide translocase (ANT) isoform genes in adipogenesis.

Adenine nucleotide translocases (ANTs) are mitochondrial proteins encoded by nuclear DNA that catalyze the exchange of ATP generated in the mitochondria for ADP produced in cytosol. There are four ANT isoforms in humans (hANT1-4) and three in mice (mANT1, mANT2 and mANT4), all encoded by distinct genes. The aim of this study was to quantify expression of ANT isoform genes during the adipogenesis of mouse 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS)-derived preadipocytes.

Expression of adenine nucleotide translocase (ANT) isoform genes is controlled by PGC-1α through different transcription factors.

Adenine nucleotide translocase (ANT) isoforms are mitochondrial proteins encoded by nuclear DNA that catalyze the exchange of ATP generated in the mitochondria for ADP produced in the cytosol. The aim of this study was to determine the role of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor-γ [PPAR-γ] coactivator 1α), a master regulator of mitochondrial oxidative metabolism, in the regulation of the expression of ANT isoform genes and to identify the transcription factors involved. We found that PGC-1α overexpression induced the expression of all ANT human and mouse isoforms but to different degrees.

Apoptotic and anti-proliferative effects of all-trans retinoic acid. Adenine nucleotide translocase sensitizes HeLa cells to all-trans retinoic acid.

We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation.

Recruitment of NF-kappaB into mitochondria is involved in adenine nucleotide translocase 1 (ANT1)-induced apoptosis.

Overexpression of adenine nucleotide translocase-1 (ANT1) is known to induce apoptosis (Bauer, M. K., Schubert, A.

Adenine nucleotide translocase 3 (ANT3) overexpression induces apoptosis in cultured cells.

Mitochondrial adenine nucleotide translocase 1 (ANT1), but not ANT2, can dominantly induce apoptosis. Nothing is known, however, about the apoptotic activity of ANT3. We have transfected HeLa cells with the three human ANT isoforms to compare their potential as inducers of apoptosis.

Assessment of membrane-bound mammal mitochondrial adenine nucleotide translocase topography by experimental antibodies.

To gain insight into the immunogenicity of mitochondrial adenine nucleotide translocase (ANT), we raised antibodies against purified bovine heart ANT by induction of ascitic fluid in male Balb/c mice. We identified the antigenic determinants detected by these antibodies by (1) immunodetection of GST-ANT fusion proteins and selected partial constructs of ANT, (2) immunodetection of chemically synthesized overlapping peptides on solid support, and (3) back-titration ELISA. Results revealed a short epitope spreading of the antibodies, resulting in a small number of antigenic determinants.

All-trans-retinoic acid binds to and inhibits adenine nucleotide translocase and induces mitochondrial permeability transition.

We investigated the effects of retinoic acids on mitochondrial permeability transition (MPT) measured as changes in rhodamine 123 fluorescence from both isolated heart mitochondria and HeLa cells. We report that all-trans-retinoic acid (atRA), 9-cis-retinoic acid, and 13-cis-retinoic acid induce a drop in mitochondrial membrane potential in isolated mitochondria. The atRA effect was done through the induction of MPT because it was dependent on Ca(2+), in a synergic mechanism, and inhibited by cyclosporin A (CsA).

Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.

Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT).