Molecular characterization of carnitine-dependent transport of acetyl-CoA from peroxisomes to mitochondria in Saccharomyces cerevisiae and identification of a plasma membrane carnitine transporter, Agp2p

被引:147
作者
van Roermund, CWT
Hettema, EH
van den Berg, M
Tabak, HF
Wanders, RJA
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, NL-1100 DE Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Biochem, NL-1100 DE Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Paediat, Emma Childrens Hosp, NL-1100 DE Amsterdam, Netherlands
关键词
acetyl-CoA; beta-oxidation; carnitine; fatty acids; peroxisomes;
D O I
10.1093/emboj/18.21.5843
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In Saccharomyces cerevisiae, beta-oxidation of fatty acids is confined to peroxisomes. The acetyl-CoA produced has to be transported from the peroxisomes via the cytoplasm to the mitochondrial matrix in order to be degraded to CO2 and H2O. Two pathways for the transport of acetyl-CoA to the mitochondria have been proposed. The first involves peroxisomal conversion of acetyl-CoA into glyoxylate cycle intermediates followed by transport of these intermediates to the mitochondria. The second pathway involves peroxisomal conversion of acetyl-CoA into acetylcarnitine, which is subsequently transported to the mitochondria. Using a selective screen, we have isolated several mutants that are specifically affected in the second pathway, the carnitine-dependent acetyl-CoA transport from the peroxisomes to the mitochondria, and assigned these CDAT mutants to three different complementation groups. The corresponding genes were identified using functional complementation of the mutants with a genomic DNA library In addition to the previously reported carnitine acetyl-CoA transferase (CAT2), we identified the genes for the yeast orthologue of the human mitochondrial carnitine acylcarnitine translocase (YOR100C or CAC) and for a transport protein (AGP2) required for carnitine transport across the plasma membrane.
引用
收藏
页码:5843 / 5852
页数:10
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