Fatty acid import into mitochondria

Biochim Biophys Acta. 2000 Jun 26;1486(1):1-17. doi: 10.1016/s1388-1981(00)00044-5.


The mitochondrial carnitine system plays an obligatory role in beta-oxidation of long-chain fatty acids by catalyzing their transport into the mitochondrial matrix. This transport system consists of the malonyl-CoA sensitive carnitine palmitoyltransferase I (CPT-I) localized in the mitochondrial outer membrane, the carnitine:acylcarnitine translocase, an integral inner membrane protein, and carnitine palmitoyltransferase II localized on the matrix side of the inner membrane. Carnitine palmitoyltransferase I is subject to regulation at the transcriptional level and to acute control by malonyl-CoA. The N-terminal domain of CPT-I is essential for malonyl-CoA inhibition. In liver CPT-I activity is also regulated by changes in the enzyme's sensitivity to malonyl-CoA. As fluctuations in tissue malonyl-CoA content are parallel with changes in acetyl-CoA carboxylase activity, which in turn is under the control of 5'-AMP-activated protein kinase, the CPT-I/malonyl-CoA system is part of a fuel sensing gauge, turning off and on fatty acid oxidation depending on the tissue's energy demand. Additional mechanism(s) of short-term control of CPT-I activity are emerging. One proposed mechanism involves phosphorylation/dephosphorylation dependent direct interaction of cytoskeletal components with the mitochondrial outer membrane or CPT-I. We have proposed that contact sites between the outer and inner mitochondrial membranes form a microenvironment which facilitates the carnitine transport system. In addition, this system includes the long-chain acyl-CoA synthetase and porin as components.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Biological Transport
  • Carnitine / metabolism
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Coenzyme A Ligases / metabolism
  • Fatty Acids / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Intracellular Membranes / metabolism*
  • Malonyl Coenzyme A / metabolism
  • Mitochondria / metabolism*
  • Oxidation-Reduction
  • Porins / metabolism
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Structure-Activity Relationship


  • Fatty Acids
  • Porins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Malonyl Coenzyme A
  • Carnitine O-Palmitoyltransferase
  • Coenzyme A Ligases
  • FAA2 protein, S cerevisiae
  • long-chain-fatty-acid-CoA ligase
  • Carnitine