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Duramycin effects on the structure and function of heart mitochondria. I. Structural alterations and changes in
P M Sokolove1, P A Westphal, M B Kester
1Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, Baltimore.
Abstract:
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.
Insights
Duramycin, an antibiotic, alters mitochondrial structure and membrane permeability by interacting with phosphatidylethanolamine (PE). It causes contraction, swelling, and membrane separation, with effects on permeability mediated by the adenine nucleotide translocator.
Area of Science:
- Mitochondrial biology
- Membrane biophysics
- Pharmacology
Background:
- Duramycin is a polypeptide antibiotic known to interact with specific lipids.
- Phosphatidylethanolamine (PE) is a crucial lipid component of mitochondrial membranes.
Purpose of the Study:
- To investigate the role of PE in mitochondrial structure and membrane permeability using duramycin.
- To elucidate the mechanism of duramycin's effects on mitochondrial membranes.
Main Methods:
- Isolated rat heart mitochondria were treated with duramycin.
- Changes in mitochondrial morphology (contraction, swelling, membrane separation) were observed.
- Mitochondrial inner membrane permeability to cations and small solutes was assessed.
Main Results:
- Duramycin induced mitochondrial contraction followed by swelling and outer membrane ruffling/separation.
- Low duramycin concentrations selectively increased inner membrane permeability, an effect inhibited by adenine nucleotide translocator inhibitors.
- Higher duramycin concentrations caused a generalized permeability increase, unaffected by these inhibitors.
Conclusions:
- Duramycin significantly impacts mitochondrial structure and membrane integrity.
- The adenine nucleotide translocator plays a key role in duramycin-induced selective permeability changes in the inner mitochondrial membrane.
- Duramycin serves as a valuable tool for studying PE's role in mitochondrial function.