Effects of fusaric acid on rat liver mitochondria.

The effects of fusaric acid on hepatic energy metabolism were measured. Three experimental systems were employed: (a) Intact rat liver mitochondria; (b) freeze-thawing disrupted mitochondria; and (c) the isolated perfused rat liver. Fusaric acid affects mitochondrial energy metabolism by at least three modes of action: (1) Inhibition of succinate-dehydrogenase (in the 10(-3)-10(-2) M range); (2) inhibition of oxidative phosphorylation (in the 10(-5)-10(-4) M range); and (3) inhibition of alpha-ketoglutarate-dehydrogenase (in the 10(-5)-10(-4) M range). The inhibition of oxidative phosphorylation seems to be the result of a direct action on the ATP-synthase/ATPase without significant inhibition of the ATP/ADP exchange. In the isolated perfused rat liver, fusaric acid inhibits oxygen uptake and gluconeogenesis from pyruvate, the latter being strictly dependent on intramitochondrially generated ATP. The effects of fusaric acid on rat liver mitochondria are similar to those reported previously for maize root mitochondria. However, except for the action on succinate-dehydrogenase, rat liver mitochondria are approximately two orders of magnitude more sensitive than maize root mitochondria.