Duramycin effects on the structure and function of heart mitochondria. I. Structural alterations and changes in membrane permeability.
The polypeptide antibiotic duramycin has been reported to interact specifically with two lipids: phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (Navarro et al. (1985) Biochemistry 24, 4645-4650). PE is a major component of mitochondrial membranes. Duramycin was used to examine the role of PE in maintenance of mitochondrial structure and membrane permeability properties with the following results: (1) Duramycin addition to isolated rat heart mitochondria produced abrupt organelle contraction which was followed, depending on composition of the suspending medium, by pronounced swelling. The most notable morphological effect of the antibiotic was ruffling or crenelation of the outer membrane, which resulted ultimately in its separation from the inner membrane. (2) Low concentrations (less than 5 microM) of the antibiotic selectively increased the permeability of the mitochondrial inner membrane to cations and small solutes. This effect was blocked by atractyloside, a highly specific inhibitor of the adenine nucleotide translocator, by palmitoyl coenzyme A, by N-ethylmaleimide, and by AMP, ADP and ATP but not GDP or GTP, implicating the adenine nucleotide translocator in the selective permeability increase. (3) Higher concentrations of duramycin induced a more generalized permeability increase which was not subject to inhibition by compounds capable of interacting with the adenine nucleotide translocator.
Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, Baltimore.
P M
PM
Sokolove
P A
PA
Westphal
M B
MB
Kester
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R
Wierwille
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Sikora-VanMeter
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010539:Permeability; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013696:Temperature
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; D012402:Rotenone; C040522:duramycin