ABCC6 localizes to the mitochondria-associated membrane

Circ Res. 2012 Aug 17;111(5):516-20. doi: 10.1161/CIRCRESAHA.112.276667. Epub 2012 Jul 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Biotinylation
  • Calcinosis / genetics
  • Calcinosis / metabolism*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cell Fractionation
  • Cell Respiration / physiology
  • Gene Expression Regulation / physiology
  • Genes, Mitochondrial / physiology
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Multidrug Resistance-Associated Proteins
  • Pseudoxanthoma Elasticum / genetics
  • Pseudoxanthoma Elasticum / metabolism*


  • ATP-Binding Cassette Transporters
  • Abcc6 protein, mouse
  • Multidrug Resistance-Associated Proteins