title: L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria.
abstract: Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca(2+) transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation.
authors.affiliation: Department of Cytology & Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Shikata, Okayama, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Oyanagi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kato
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujita
authors.forename: Kozo
authors.initials: K
authors.lastname: Utsumi
authors.forename: Junzo
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D002509:Cephaloridine / Q000494:pharmacology; D003065:Coenzyme A / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D019301:Oleic Acid / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D020011:Protective Agents; D019301:Oleic Acid; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D002509:Cephaloridine; D002331:Carnitine; D003065:Coenzyme A