Enhanced uptake of spermidine and methylglyoxal-bis(guanylhydrazone) by rat liver mitochondria following outer membrane lysis.
Isolated rat liver mitochondria rapidly bound the 14C-labeled organic cations spermidine, a physiologically important polyamine, and methylglyoxal-bis(guanylhydrazone) (MGBG), an anticancer drug. This rapid, Mg2+-sensitive, respiration-independent binding is assumed to involve adsorption to anionic surface groups. A slower progressive uptake of the organic cations exhibited respiration dependence, indicating that it involves transport across the inner mitochondrial membrane into the matrix compartment. Addition of digitonin, to lyse the outer mitochondrial membrane, caused an increase in the mitochondrial content of the organic cations and enhanced the rate of progressive, respiration-dependent cation uptake. The data are consistent with the interpretation that the outer mitochondrial membrane limits access of the organic cations, spermidine and MGBG, to the inner mitochondrial membrane. This conclusion is supported also by published data indicating that outer membrane lysis enhances inhibitory effects of the organic cations on mitochondrial respiration. The uptake of spermidine by mitochondria was inhibited by MGBG.
Diwan
J J
JJ
Biology Department, Rensselaer Polytechnic Institute, Troy, NY 12180-3590.
Yune
H H
HH
Bawa
R
R
Haley
T
T
Mannella
C A
CA
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D004072:Digitonin / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008935:Mitoguazone / Q000493:pharmacokinetics*; D010539:Permeability; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000493:pharmacokinetics*
D000968:Antimycin A; D008274:Magnesium; D004072:Digitonin; D008935:Mitoguazone; D011188:Potassium; D013095:Spermidine