Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition.
Palmitoyl-CoA (Pal-CoA) lowered the respiratory control ratio (RCR), and induced mitochondrial membrane permeability transition (MPT) and cytochrome c (Cyt. c) release from isolated rat liver mitochondria. L-Carnitine suppressed the Pal-CoA-induced dysfunction, MPT, and Cyt. c release of isolated mitochondria. This suppression was inhibited by cephaloridine, an inhibitor of carnitine uptake into mitochondria. Cyclosporin A (CsA), an inhibitor of MPT, and BSA also suppressed the Pal-CoA-induced MPT. In the presence of inorganic phosphate (P(i)), Ca2+-induced MPT was suppressed by BSA, L-carnitine, and chlorpromazine, an inhibitor of phospholipase A2. In the presence of a low concentration of Ca2+, 3,3',5-triiodothyronine, long chain fatty acids, salicylic acid, and diclofenac induced MPT by a mechanism that was suppressed by BSA, L-carnitine, or chlorpromazine. During the incubation of mitochondria on ice, their respiratory competence decreased; L-carnitine and BSA also prevented this decrease. Mitochondrial depolarization in pheochromocytoma PC12 cells was induced by either serum deprivation or arachidonic acid by a mechanism that was suppressed by acetyl-L-carnitine. These results indicate that some MPTs may be regulated by fatty acid metabolism and that the Pal-CoA-induced MPT plays an important role in the induction of apoptosis.
Furuno
T
T
Department of Medicine and Gerontology, Kochi Medical School, Japan.
Kanno
T
T
Arita
K
K
Asami
M
M
Utsumi
T
T
Doi
Y
Y
Inoue
M
M
Utsumi
K
K
D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D016922:Cellular Senescence / Q000187:drug effects; D002509:Cephaloridine / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D016716:PC12 Cells; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D002511:Cephalosporins; D003574:Cytochrome c Group; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D010171:Palmitoyl Coenzyme A; D012710:Serum Albumin, Bovine; D016572:Cyclosporine; D002509:Cephaloridine; D002331:Carnitine; D002746:Chlorpromazine