Palmitic Acid Opens a Novel Cyclosporin A-Insensitive Pore in the Inner Mitochondrial Membrane

摘要: An assortment of agents can induce mitochondria to undergo a permeability transition, which results in the inner mitochondrial membrane becoming nonselectively permeable small (<1500 Da) solutes. This transition (MPT) is characterized by strict dependence on matrix Ca2+ and sensitivity cyclosporin A (CsA). However, it increasingly clear that other experimental conditions elicit increases are distinct from this classic MPT. For example, butylated hydroxytoluene (BHT; Sokolove, P. M., Haley, L. M. (1996) J. Bioenerg. Biomembr. 28, 199–206) signal peptides (Sokolove, Kinnally, K. W. Arch. Biochem. Biophys. 336, 69–76) promote CsA-insensitive. It has been suggested (Gudz, T., Eriksson, O., Kushnareva, Y., Saris, N.-E., Novgorodov, S. A. (1997) 342, 143–156) BHT might be opening CsA-insensitive pore increasing phospholipase A2 activity thereby producing an accumulation free fatty acids lysophospholipids. We have therefore examined effect saturated acid, palmitic acid (PA), isolated rat liver mitochondria. The following were obtained: (1) In absence additional triggers, PA (20–60 μM) induced concentration-dependent, swelling. (2) Swelling required energization. (3) PA-induced swelling was fast occurred without lag. (4) Both Sr2+ supported swelling; site cation action matrix. (5) EGTA BSA potent inhibitors (6) opened rather than disrupting structure. (7) closed spontaneously. These suggest promotes nonclassic increase clearly distinguishable occurrence