Inhibition of respiration in mitochondria and in digitonin-treated rat hepatocytes by podophyllotoxin.
The effects of the microtubular inhibitor, podophyllotoxin, on mitochondrial respiration were determined using isolated, digitonin-permeabilized hepatocytes and isolated mitochondria. In hepatocytes, podophyllotoxin (1.5 mM) inhibited coupled and uncoupled respiration of both FAD and NAD-linked substrates. In mitochondria, podophyllotoxin inhibited State III respiration, prevented the return to State IV respiration, and inhibited uncoupled respiration. There was no inhibition of ascorbate/TMPD oxidation in either the hepatocytes or the mitochondria. Podophyllotoxin had no effect upon oligomycin inhibition of coupled respiration. Oligomycin had no effect on the podophyllotoxin-inhibition of uncoupled respiration in either hepatocytes or mitochondria. The results indicate that podophyllotoxin alters electron flow at a site early in the electron transport chain.
D000818:Animals; D004072:Digitonin / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011034:Podophyllotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014475:Uncoupling Agents / Q000494:pharmacology
D014475:Uncoupling Agents; D004072:Digitonin; D011034:Podophyllotoxin