Protective action of l-carnitine on cardiac mitochondrial function and structure against fatty acid stress |
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Authors: | Eri Oyanagi Hiromi Yano Masataka Uchida Kozo Utsumi Junzo Sasaki |
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Institution: | aDepartment of Cytology and Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;bDepartment of Health and Sports Science, Kawasaki University of Medical Welfare, Kurashiki, Japan |
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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. |
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Keywords: | Palmitoyl-CoA β-Oxidation Cytochrome c Heart |
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