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., Rocks, O., and Grimm, S. (1999) J. Cell Biol. 147, 1493-1501), but the mechanisms involved remain unclear. In this study we show that ANT1 overexpression results in a recruitment of the IkappaBalpha-NF-kappaB complex into mitochondria, with a coincident decrease in nuclear NF-kappaB DNA binding activity. In this situation, NF-kappaB transcriptionally regulated genes with antiapoptotic activity, such as Bcl-XL, MnSOD2, and c-IAP2, are down-regulated, and consequently, cells are sensitized to apoptosis. Accordingly, co-expression of p65 partially interferes with the proapoptotic effect of ANT1 overexpression. Despite the high identity of the two isoforms, overexpression of ANT2 does not exert an apoptotic effect; this lack of apoptotic activity is correlated with the absence of mitochondrial IkappaBalpha-NF-kappaB recruitment or changes in NF-kappaB activity. Thus, we propose that the mitochondrial recruitment of NF-kappaB observed following ANT1 overexpression has an important role in ANT1 proapoptotic activity.
Zamora
Monica
M
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Diagonal 645, 08028 Barcelona, Spain.
Meroño
Claudia
C
Viñas
Octavi
O
Mampel
Teresa
T
D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism*; D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism*; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D019286:Endopeptidase K / Q000494:pharmacology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions; D014158:Transcription, Genetic; D014162:Transfection
D033741:Adenine Nucleotide Translocator 1; D033742:Adenine Nucleotide Translocator 2; D017304:Annexin A5; D004396:Coloring Agents; D018076:DNA, Complementary; D016328:NF-kappa B; D012333:RNA, Messenger; D004247:DNA; D019286:Endopeptidase K; D016650:Fluorescein-5-isothiocyanate