title: Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery.
abstract: Lethal mitochondrial membrane permeabilization has been depicted as the result of two fundamentally distinct processes, namely primary mitochondrial outer membrane permeabilization (MOMP) versus permeability transition (PT) ignited at the level of the mitochondrial inner membrane. MOMP and PT have been connected to apoptosis and necrosis, respectively. Moreover, it has been thought that MOMP was mediated by pro-apoptotic multidomain proteins of the Bcl-2 family (Bax and Bak), which would operate near-to-independently from the permeability transition pore complex (PTPC) composed by voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT) and cyclophilin D. A recent paper in Molecular and Cellular Biology now reveals the obligate contribution of one particular ANT isoform to the execution of developmental and homeostatic cell death in Caenorhabditis elegans. The physical and functional interaction between CED-9, the sole multidomain Bcl-2 protein of C. elegans, and ANT emphasizes the existence of an intricate, phylogenetically conserved crosstalk between Bcl-2 family proteins and constituents of the PTPC. In this issue of Cell Death and Differentiation, Malorni et al. further corroborate this notion by showing that type 2 transglutaminase (TG2) is essential for the correct assembly/function of ANT1, and that, at least in some experimental settings, TG2 might be required to enable and/or stabilize the pro-apoptotic association of Bax with ANT1.
authors.affiliation: Division of Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: L
authors.initials: L
authors.lastname: Galluzzi
authors.forename: O
authors.initials: O
authors.lastname: Kepp
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D016923:Cell Death; D019204:GTP-Binding Proteins / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000145:classification / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010802:Phylogeny; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D000226:Mitochondrial ADP, ATP Translocases; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins