Inhibition of respiration in mitochondria and in digitonin-treated rat hepatocytes by podophyllotoxin |
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Authors: | Mark A Horrum Richard B Jennett Robert E Ecklund Richard B Tobin |
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Institution: | (1) Department of Internal Medicine, University of Nebraska Medical Center and Veterans Administration Medical Center, 68105 Omaha, NB, USA;(2) Research Service, Veterans Administration Medical Center, 4101 Woolworth Avenue, 68105 Omaha, NE, USA |
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Abstract: | Summary 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. |
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Keywords: | Podophyllotoxin mitochondria hepatocytes respiration |
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