Suramin inhibits respiration and induces membrane permeability transition in isolated rat liver mitochondria

Suramin, a polysulfonated naphthylamine. caused a dose dependent inhibition of carbonyl cyanide p-(trifluoromethoxy)phenyihydrazone-stimulated respira tion supported either by succinate or a cocktail of alpha ketoglutarate, ma late and isocitrate in isolated rat liver mitochondria. The half-maximum ef fect was obtained at 40 and 140 muM suramin for NADH- or FADH(2)-linked sub strates, respectively. The respiration supported by N,N,,N'N'-tetramethyl-p -phenylenediamine oxidation was unaffected by suramin (less than or equal t o 500 muM). The latter respiratory substrate was used in the studies at exa mining the effects of suramin on the permeability properties of the inner m itochondrial membrane. These experiments provided evidence that suramin cau ses Ca2+-dependent mitochondrial swelling sensitive to the mitochondrial pe rmeability transition (MPT) inhibitors cyclosporin A, ADP and Mg2+. In addi tion, suramin decreased the content of reduced mitochondrial membrane prote in thiols suggesting that thiol oxidation is the mechanism underlying suram in-induced MPT. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.