Peroxisomes contribute to the acylcarnitine production when the carnitine shuttle is deficient

Sara Violante, Lodewijk IJlst, Heleen Te Brinke, Janet Koster, Isabel Tavares De Almeida, Ronald J.A. Wanders, Fátima V. Ventura, Sander M. Houten

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Fatty acid â-oxidation may occur in bothmitochondria 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 β-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatorymechanismtometabolize straightmediumand long-chain fatty acids, especially in cases of mitochondrial fatty acid β-oxidation deficiency or overload.

Original languageEnglish
Pages (from-to)1467-1474
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number9
StatePublished - 2013
Externally publishedYes


  • Carnitine palmitoyltransferase 1
  • Carnitine palmitoyltransferase 2
  • Carnitine/acylcarnitine translocase
  • Fatty acid β-oxidation
  • Medium-chain fatty acids
  • Mitochondria


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