OCTN3 is a mammalian peroxisomal membrane carnitine transporter
- Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto (Canada)
- Department of Pathology, Hospital for Sick Children, Toronto (Canada)
- Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)
- Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto (Canada) and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ont., M5G 1X8 (Canada)
Carnitine is a zwitterion essential for the {beta}-oxidation of fatty acids. The role of the carnitine system is to maintain homeostasis in the acyl-CoA pools of the cell, keeping the acyl-CoA/CoA pool constant even under conditions of very high acyl-CoA turnover, thereby providing cells with a critical source of free CoA. Carnitine derivatives can be moved across intracellular barriers providing a shuttle mechanism between mitochondria, peroxisomes, and microsomes. We now demonstrate expression and colocalization of mOctn3, the intermediate-affinity carnitine transporter (K {sub m} 20 {mu}M), and catalase in murine liver peroxisomes by TEM using immunogold labelled anti-mOctn3 and anti-catalase antibodies. We further demonstrate expression of hOCTN3 in control human cultured skin fibroblasts both by Western blotting and immunostaining analysis using our specific anti-mOctn3 antibody. In contrast with two peroxisomal biogenesis disorders, we show reduced expression of hOCTN3 in human PEX 1 deficient Zellweger fibroblasts in which the uptake of peroxisomal matrix enzymes is impaired but the biosynthesis of peroxisomal membrane proteins is normal, versus a complete absence of hOCTN3 in human PEX 19 deficient Zellweger fibroblasts in which both the uptake of peroxisomal matrix enzymes as well as peroxisomal membranes are deficient. This supports the localization of hOCTN3 to the peroxisomal membrane. Given the impermeability of the peroxisomal membrane and the key role of carnitine in the transport of different chain-shortened products out of peroxisomes, there appears to be a critical need for the intermediate-affinity carnitine/organic cation transporter, OCTN3, on peroxisomal membranes now shown to be expressed in both human and murine peroxisomes. This Octn3 localization is in keeping with the essential role of carnitine in peroxisomal lipid metabolism.
- OSTI ID:
- 20793249
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 338, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2005.10.170; PII: S0006-291X(05)02464-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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