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ABCC6 Localizes to the Mitochondria-Associated Membrane

Year: 2012
Type: article
Abstract: 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.
DOI: 10.1161/circresaha.112.276667
Authors: Lisa J. Martin, Edward Lau, Harpreet Singh, Laurent Vergnes, Elizabeth J. Tarling, Margarete Mehrabian, Imran Mungrue, Sheila Xiao, Diana Shih, Lawrence Castellani, Peipei Ping, Karen Reue, Enrico Stefani, Thomas A. Drake, Kristina Bostrom, Aldons J. Lusis
Language: English
Subfield: Genetics
Open Access status: green
Awards: G1218651441, G1418530609, G1553163121, XF24-3 Extracellular Flux Analyzer, Dissection of HDL function using mouse models, G3206989158, G3360134629, G3604227628, Determining roles of the pro-apoptotic UPR gene CHAC1 in atherosclerosis., G6519275499
OpenAlex ID: W2040901772
FWCI: 4.071
Cites: 15
Cited by: 46
Related to: 10