L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria.
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.
Oyanagi
Eri
E
Department of Cytology & Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Shikata, Okayama, Japan.
Yano
Hiromi
H
Kato
Yasuko
Y
Fujita
Hirofumi
H
Utsumi
Kozo
K
Sasaki
Junzo
J
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
D020011:Protective Agents; D019301:Oleic Acid; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D002509:Cephaloridine; D002331:Carnitine; D003065:Coenzyme A