Protective action of L-carnitine on cardiac mitochondrial function and structure against fatty acid stress

Biochem Biophys Res Commun. 2011 Aug 19;412(1):61-7. doi: 10.1016/j.bbrc.2011.07.039. Epub 2011 Jul 21.

Abstract

Cardiovascular risks are frequently accompanied by high serum fatty acid levels. Although recent studies have shown that fatty acids affect mitochondrial function and induce cell apoptosis, L-carnitine is essential for the uptake of fatty acids by mitochondria, and may attenuate the mitochondrial dysfunction and apoptosis of cardiocytes. This study aimed to elucidate the activity of L-carnitine in the prevention on fatty acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoyl-CoA-induced mitochondrial respiration that was observed with L-carnitine was inhibited with oligomycin. The palmitoyl-CoA-induced mitochondrial membrane depolarization and swelling were greatly inhibited by the presence of L-carnitine. In ultrastructural observations, terminally swollen and ruptured mitochondria with little or no distinguishable cristae structures were induced by treatment with palmitoyl-CoA. However, the severe morphological damage in cardiac mitochondria was dramatically inhibited by pretreatment with L-carnitine. Treatment with L-carnitine also attenuated 4-hydroxy-L-phenylglycine- and rotenone-induced mitochondrial swelling even when the L-carnitine could not protect against the decrease in oxygen consumption associated with these inhibitors. Furthermore, L-carnitine completely inhibited palmitoyl-CoA-induced cytochrome c release. We concluded that L-carnitine is essential for cardiac mitochondria to attenuate the membrane permeability transition, and to maintain the ultrastructure and membrane stabilization, in the presence of high fatty acid β-oxidation. Consequently, the cells may be protected against apoptosis by L-carnitine through inhibition of the fatty acid-induced cytochrome c release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnitine / pharmacology*
  • Fatty Acids / pharmacology*
  • Mitochondria, Heart / ultrastructure
  • Mitochondrial Swelling / drug effects*
  • Oxygen Consumption / drug effects
  • Palmitoyl Coenzyme A / pharmacology
  • Permeability / drug effects
  • Rats
  • Stress, Physiological / drug effects*
  • Vitamin B Complex / pharmacology*

Substances

  • Fatty Acids
  • Vitamin B Complex
  • Palmitoyl Coenzyme A
  • Carnitine