ABCC6 Localizes to the Mitochondria-Associated Membrane
Rationale: Mutations of the orphan transporter ABCC6 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 (MAM) fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-KO mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity.
Conclusions: Our finding that ABCC6 localizes to the MAM has implications for its mechanism of action in normal and diseased states.
- Received June 28, 2012.
- Accepted July 17, 2012.
- Copyright © 2012, American Heart Association