Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1831, Issue 9, Pages 1467-1474Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2013.06.007
Keywords
Fatty acid beta-oxidation; Mitochondria; Medium-chain fatty acids; Carnitine palmitoyltransferase 1; Carnitine palmitoyltransferase 2; Carnitine/acylcarnitine translocase
Funding
- Fundacao para a Ciencia e Tecnologia (FCT), Lisboa, Portugal
- Netherlands Organization for Scientific Research (VIDI-grant) [016.086.336]
- [SFRH/BD/38074/2007]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/38074/2007] Funding Source: FCT
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Fatty acid beta-oxidation may occur in both mitochondria and peroxisomes. While peroxisomes oxidize specific carboxylic acids such as very long-chain fatty acids, branched-chain fatty acids, bile acids, and fatty dicarboxylic acids, mitochondria oxidize long-, medium-, and short-chain fatty acids. Oxidation of long-chain substrates requires the carnitine shuttle for mitochondrial access but medium-chain fatty acid oxidation is generally considered carnitine-independent Using control and carnitine palmitoyltransferase 2 (CPT2)- and carnitine/acylcarnitine translocase (CACT)-deficient human fibroblasts, we investigated the oxidation of lauric acid (C12:0). Measurement of the acylcarnitine profile in the extracellular medium revealed significantly elevated levels of extracellular C10- and C12-carnitine in CPT2- and CACT-deficient fibroblasts. The accumulation of C12-carnitine indicates that lauric acid also uses the carnitine shuttle to access mitochondria. Moreover, the accumulation of extracellular C10-carnitine in CPT2- and CACT-deficient cells suggests an extramitochondrial pathway for the oxidation of lauric acid. Indeed, in the absence of peroxisomes C10-carnitine is not produced, proving that this intermediate is a product of peroxisomal beta-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatory mechanism to metabolize straight medium- and long-chain fatty acids, especially in cases of mitochondrial fatty acid beta-oxidation deficiency or overload. (C) 2013 Elsevier B.V. All rights reserved.
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