Free fatty acid effects on mitochondrial permeability: an overview
| Autor: | Aya Sultan, Patricia M. Sokolove |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Biophysics Palmitic Acid Mitochondria Liver Fatty Acids Nonesterified Biochemistry Divalent Palmitic acid Rats Sprague-Dawley chemistry.chemical_compound Cytosol Cyclosporin a medicine Butylated hydroxytoluene Animals Enzyme Inhibitors Inner mitochondrial membrane Molecular Biology chemistry.chemical_classification Fatty acid Mitochondria Rats Electrophysiology chemistry Mitochondrial permeability transition pore Spectrophotometry Strontium Cyclosporine lipids (amino acids peptides and proteins) Calcium Swelling medicine.symptom |
| Zdroj: | Archives of biochemistry and biophysics. 386(1) |
| ISSN: | 0003-9861 |
| Popis: | A variety of experimental conditions elicit increases in mitochondrial permeability that can be differentiated from the classic cyclosporin A (CsA)-sensitive mitochondrial permeability transition (MPT). For example, butylated hydroxytoluene, signal peptides, and the hormone thyroxine have been shown to promote increases in mitochondrial permeability that are CsA-insensitive. Our laboratory has recently demonstrated that palmitic acid, a saturated 16-carbon free fatty acid (FFA), can also open a CsA-insensitive pore. This nonclassic permeability transition (NCPT) is further distinguished by a nonselective dependence on divalent cations and by spontaneous closure. To determine if induction of the NCPT is specific to palmitic acid and to resolve conflicting reports as to the mechanisms by which FFAs alter mitochondrial permeability, we examined in detail mitochondrial swelling induced by FFAs that differ in chain length and degree of saturation. The following results were obtained: (1) In the presence of modest Ca2+ concentrations (75 nmol/mg protein), medium-chain FFAs (C12–C18) were more effective in eliciting mitochondrial swelling than were shorter or longer FFAs; medium-chain alkanols and amines had no effect. (2) Under these conditions, saturated FFAs induced CsA-insensitive swelling with all the characteristics of the NCPT, while unsaturated FFAs triggered the MPT. (3) When matrix Ca2+ concentration was further elevated, unsaturated FFAs triggered the NCPT. (4) Mitochondrial swelling induced by saturated FFAs was inhibited by unsaturated FFAs but not by other saturated FFAs or medium-chain alkanols. These results suggest that ambient conditions can greatly influence the nature of the increase in mitochondrial permeability induced by FFAs. They are also consistent with our earlier proposal that Ca2+ (or Sr2+) binding to FFAs in the inner leaflet of the inner mitochondrial membrane underlies the NCPT. |
| Databáze: | OpenAIRE |
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