Action of rubratoxin B on mouse liver mitochondria

The effect of rubratoxin B on the electron transport system of mouse liver mitochondria was investigated. Oxygen consumption in mitochondria isolated from male mice was measured polarographically in a Gilson Oxygraph Model K-ICC. Oxygen consumption was depressed 73% at a concentration of 1.13 mM rubratoxin. At concentrations as low as 0.08 mM rubratoxin B, 50% inhibition was observed. Rubratoxin B (0.28 mM) depressed oxygen consumption 67% in ADP-coupled mitochondria and 60% in 2,4-dinitrophenol (DNP)-uncoupled mitochondria using either pyridine-nucleotide linked substrates or succinate. By employing the N,N,N',N''-tetramethyl-p-phenylenediamine (TMPD) shunt, it was shown that inhibition was not between cytochrome b and cytochrome C1 or C. It appears, based on these studies and comparison with known inhibitors of specific sites along the electron transport system that the principal site of action of rubratoxin B is between cytochrome C1 or C and the termination of electron flow.