Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition

Citation
T. Furuno et al., Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition, BIOCH PHARM, 62(8), 2001, pp. 1037-1046
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1037 - 1046
Database
ISI
SICI code
0006-2952(20011015)62:8<1037:ROLCFA>2.0.ZU;2-2
Abstract
Palmitoyl-CoA (Pal-CoA) lowered the respiratory control ratio (RCR), and in duced mitochondrial membrane permeability transition (MPT) and cytochrome c (Cyt. c) release from isolated rat liver mitochondria. L-Carnitine suppres sed the Pal-CoA-induced dysfunction, MPT, and Cyt. c release of isolated mi tochondria. This suppression was inhibited by cephaloridine, an inhibitor o f carnitine uptake into mitochondria. Cyclosporin A (CsA), an inhibitor of MPT, and BSA also suppressed the Pal-CoA-induced MPT. In the presence of in organic phosphate (P-i), Ca2+-induced MPT was suppressed by BSA, L-carnitin e, and chlorpromazine, an inhibitor of phospholipase A(2). In the presence of a low concentration of Ca2+, 3,3',5-triiodothyronine, long chain fatty a cids, salicylic acid, and diclofenac induced MPT by a mechanism that was su ppressed by BSA, L-carnitine, or chlorpromazine. During the incubation of m itochondria on ice, their respiratory competence decreased; L-carnitine and BSA also prevented this decrease. Mitochondrial depolarization in pheochro mocytoma PC12 cells was induced by either serum deprivation or arachidonic acid by a mechanism that was suppressed by acetyl-L-carnitine. These result s indicate that some MPTs may be regulated by fatty acid metabolism and tha t the Pal-CoA-induced MPT plays an important role in the induction of apopt osis. (C) 2001 Elsevier Science Inc. All rights reserved.