First Author | Malorni W | Year | 2009 |
Journal | Cell Death Differ | Volume | 16 |
Issue | 11 | Pages | 1480-92 |
PubMed ID | 19644512 | Mgi Jnum | J:169279 |
Mgi Id | MGI:4940183 | Doi | 10.1038/cdd.2009.100 |
Citation | Malorni W, et al. (2009) The adenine nucleotide translocator 1 acts as a type 2 transglutaminase substrate: implications for mitochondrial-dependent apoptosis. Cell Death Differ 16(11):1480-92 |
abstractText | In this study we provide in vitro and in vivo evidence showing that the protein disulphide isomerase (PDI) activity of type 2 transglutaminase (TG2) regulates the correct assembly and function of the mitochondrial ADP/ATP transporter adenine nucleotide translocator 1 (ANT1). We demonstrate, by means of biochemical and morphological analyses, that ANT1 and TG2 physically interact in the mitochondria. Under physiological conditions, TG2's PDI activity regulates the ADP/ATP transporter function by controlling the oligomerization of ANT1. In fact, mitochondria isolated from hearts of TG2(-/-) mice exhibit increased polymerization of ANT1, paralleled by an enhanced ADP/ATP carrier activity, as compared to mitochondria belonging to TG2(+/+) mice. Interestingly, upon cell-death induction, ANT1 becomes a substrate for TG2's cross-linking activity and the lack of TG2 results in a reduction of apoptosis as well as in a marked sensitivity to the ADP/ATP exchange inhibition by atractyloside. These findings suggest a complex TG2-dependent regulation of the ADP/ATP transporter and reveal new important avenues for its potential applications in the treatment of some mitochondrial-dependent diseases, including cardiovascular and neurodegenerative diseases. |