title: ANT2 isoform required for cancer cell glycolysis.
abstract: The three adenine nucleotide translocator (ANT1 to ANT3) isoforms, differentially expressed in human cells, play a crucial role in cell bioenergetics by catalyzing ADP and ATP exchange across the mitochondrial inner membrane. In contrast to differentiated tissue cells, transformed cells, and their rho(0) derivatives, i.e. cells deprived of mitochondrial DNA, sustain a high rate of glycolysis. We compared the expression pattern of ANT isoforms in several transformed human cell lines at different stages of the cell cycle. The level of ANT2 expression and glycolytic ATP production in these cell lines were in keeping with their metabolic background and their state of differentiation. The sensitivity of the mitochondrial inner membrane potential (Deltapsi) to several inhibitors of glycolysis and oxidative phosphorylation confirmed this relationship. We propose a new model for ATP uptake in cancer cells implicating the ANT2 isoform, in conjunction with hexokinase II and the beta subunit of mitochondrial ATP synthase, in the Deltapsi maintenance and in the aggressiveness of cancer cells.
authors.affiliation: Inserm, U694, Angers, F-49033, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Dominique
authors.initials: D
authors.lastname: Loiseau
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chabi
authors.forename: Gilles
authors.initials: G
authors.lastname: Renier
authors.forename: Olivier
authors.initials: O
authors.lastname: Douay
authors.forename: Yves
authors.initials: Y
authors.lastname: Malthièry
authors.forename: Georges
authors.initials: G
authors.lastname: Stepien
mesh_terms: D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism*; D033781:Adenine Nucleotide Translocator 3 / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D006019:Glycolysis; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D033742:Adenine Nucleotide Translocator 2; D033781:Adenine Nucleotide Translocator 3; D020033:Protein Isoforms