The peroxisomal transporter ABCD3 plays a major role in dicarboxylic fatty acid metabolism
The peroxisomal transporter ABCD3 plays a major role in dicarboxylic fatty acid metabolism
Abstract Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this study, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid metabolic homeostasis. The Abcd3 KO mouse presents with lipodystrophy, increased circulating free fatty acids, decreased ketone bodies, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.
Bhattacharya Dipankar、Friedman Scott L.、Yu Chunli、Chen Hongjie、Houten Sander M.、Puchowicz Michelle、Ranea-Robles Pablo、Stauffer Brandon
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount SinaiDivision of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Mount Sinai Genomics, IncDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Mount Sinai Genomics, IncDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Nutrition, School of Medicine, Case Western Reserve University||Department of Pediatrics, University of Tennessee Health Science CenterDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Mount Sinai Genomics, Inc
基础医学生物化学生物科学研究方法、生物科学研究技术
Bhattacharya Dipankar,Friedman Scott L.,Yu Chunli,Chen Hongjie,Houten Sander M.,Puchowicz Michelle,Ranea-Robles Pablo,Stauffer Brandon.The peroxisomal transporter ABCD3 plays a major role in dicarboxylic fatty acid metabolism[EB/OL].(2025-03-28)[2025-05-31].https://www.biorxiv.org/content/10.1101/2021.07.26.452046.点此复制
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