AZT side effect on mitochondria does not depend on either inhibition of electron flow or mitochondrial uncoupling

The mitochondrial myopathy associated with long-term AZT therapy limits the clinical efficacy of this drug in AIDS therapy. Thus, in order to determine how AZT can affect mitochondria bioenergetics, the capability of AZT to both uncouple oxidative phosphorylation and inhibit electron flow in isolated rat liver mitochondria was investigated. The failure of AZT to oxidize intramitochondrial pyridine nucleotides, to stimulate mitochondrial swelling in K+-acetate plus valinomycin or to cause ATP hydrolysis shows that AZT is not an uncoupler.