RATIONALE: Mutations of the orphan transporter ABCC6 (ATP-binding cassette, subfamily C, member 6) cause the connective tissue disorder pseudoxanthoma elasticum. ABCC6 was thought to be located on the plasma membrane of liver and kidney cells. OBJECTIVE: Mouse systems genetics and bioinformatics suggested that ABCC6 deficiency affects mitochondrial gene expression. We therefore tested whether ABCC6 associates with mitochondria. METHODS AND RESULTS: We found ABCC6 in crude mitochondrial fractions and subsequently pinpointed its localization to the purified mitochondria-associated membrane fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-knockout mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity. CONCLUSIONS: Our finding that ABCC6 localizes to the mitochondria-associated membrane has implications for its mechanism of action in normal and diseased states.
RATIONALE: Mutations of the orphan transporter ABCC6 (ATP-binding cassette, subfamily C, member 6) cause the connective tissue disorder pseudoxanthoma elasticum. ABCC6 was thought to be located on the plasma membrane of liver and kidney cells. OBJECTIVE:Mouse systems genetics and bioinformatics suggested that ABCC6 deficiency affects mitochondrial gene expression. We therefore tested whether ABCC6 associates with mitochondria. METHODS AND RESULTS: We found ABCC6 in crude mitochondrial fractions and subsequently pinpointed its localization to the purified mitochondria-associated membrane fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-knockout mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity. CONCLUSIONS: Our finding that ABCC6 localizes to the mitochondria-associated membrane has implications for its mechanism of action in normal and diseased states.
Authors: Theo G M F Gorgels; Xiaofeng Hu; George L Scheffer; Allard C van der Wal; Johan Toonstra; Paulus T V M de Jong; Toin H van Kuppevelt; Christiaan N Levelt; Anneke de Wolf; Willem J P Loves; Rik J Scheper; Ron Peek; Arthur A B Bergen Journal: Hum Mol Genet Date: 2005-05-11 Impact factor: 6.150
Authors: Zouhair Aherrahrou; Lars C Doehring; Eva-Maria Ehlers; Henrike Liptau; Reinhard Depping; Patrick Linsel-Nitschke; Piotr M Kaczmarek; Jeanette Erdmann; Heribert Schunkert Journal: J Biol Chem Date: 2008-01-16 Impact factor: 5.157
Authors: Konstanze Beck; Kimiko Hayashi; Brian Nishiguchi; Olivier Le Saux; Masando Hayashi; Charles D Boyd Journal: J Histochem Cytochem Date: 2003-07 Impact factor: 2.479
Authors: Haijin Meng; Iset Vera; Nam Che; Xuping Wang; Susanna S Wang; Leslie Ingram-Drake; Eric E Schadt; Thomas A Drake; Aldons J Lusis Journal: Proc Natl Acad Sci U S A Date: 2007-03-06 Impact factor: 11.205
Authors: Emese Sinkó; Attila Iliás; Olga Ujhelly; László Homolya; George L Scheffer; Arthur A B Bergen; Balázs Sarkadi; András Váradi Journal: Biochem Biophys Res Commun Date: 2003-08-22 Impact factor: 3.575
Authors: O Le Saux; Z Urban; C Tschuch; K Csiszar; B Bacchelli; D Quaglino; I Pasquali-Ronchetti; F M Pope; A Richards; S Terry; L Bercovitch; A de Paepe; C D Boyd Journal: Nat Genet Date: 2000-06 Impact factor: 38.330
Authors: Viola Pomozi; Olivier Le Saux; Christopher Brampton; Ailea Apana; Attila Iliás; Flóra Szeri; Ludovic Martin; Katalin Monostory; Sándor Paku; Balázs Sarkadi; Gergely Szakács; András Váradi Journal: Circ Res Date: 2013-04-26 Impact factor: 17.367
Authors: Diana M Shih; Janet M Yu; Laurent Vergnes; Nassim Dali-Youcef; Matthew D Champion; Asokan Devarajan; Peixiang Zhang; Lawrence W Castellani; David N Brindley; Carole Jamey; Johan Auwerx; Srinivasa T Reddy; David A Ford; Karen Reue; Aldons J Lusis Journal: FASEB J Date: 2014-12-04 Impact factor: 5.191