Mitochondrial swelling and phospholipid splitting induced by snake venoms

Abstract

Summary 1. Purified preparations of phospholipase A (phosphatide acylhydrolase, EC 3.1.1.4) derived from Ringhals cobra venom induced pronounced swelling of rat-liver mitochondria, which was associated with a rapid breakdown of the membrane phospholipids to the corresponding lysophosphatides and free fatty acids. 2. Vipera palestinae venom and its phospholipase A, failed to affect the phospholipids and to promote swelling of the mitochondria, unless supplemented with direct lytic factor, a basic protein component of the cobra venom. 3. EDTA, known to inhibit phospholipase A by Ca 2+ sequestration, was found to suppress in a parallel manner both the phospholipid splitting and the swelling activity of the enzyme preparation. 4. The above correlations support the conclusion that the breakdown of the membrane phospholipids plays a primary role in the chain of events underlying the swelling phenomenon. 5. The partial protection afforded by serum albumin against the phospho-lipase-induced swelling appears to be attributable to its capacity for binding the free fatty acids released in the course of phospholipid splitting. 6. Some aspects of the mechanism involved in the synergistic interaction between direct lytic factor and the V. palestinae phospholipase are discussed in the light of the available data.