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

Furuno, T Kanno, T Arita, K Asami, M Utsumi, T Doi, Y Inoue, M Utsumi, K

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

46

INGLESE

Article

Pharmacology & Toxicology

BIOCHEMICAL PHARMACOLOGY

0006-2952 → ACNP

62

8

2001

1037 - 1046

ISI

0006-2952(20011015)62:8<1037:ROLCFA>2.0.ZU;2-2

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.