The locus of action in trialkyl tin compounds in yeast mitochondria

Abstract

Trialkyl tin compounds have been shown to be potent inhibitors of the yeast mitochondrial OS-ATPase complex in both the membrane bound form and purified soluble preparation. Binding studies with 11^Sn labelled triethyl tin have shown that the inhibitory properties of triethyl tin are due to the presence of a high affinity binding site which is not competed for by oligomycin or venturicidin. Die concent­ration of the binding site in the purified enzyme is 6mole/mole enzyme, the binding site has been shown to be located on the FQ component of the OS-ATPase complex. A new radioactive affinity label (DBCT) for trialkyl tin compounds has been synthesized, binding experiments revealed that DBCT is a covalent inhibitor of the OS-ATPase. Extraction and isolation experi­ments have shown that DBCT binds to a small lipophilic, apparently non-protein component of the mitochondrial membrane. The significance of these findings are discussed in relation to current ideas on oxidative phosphorylation. A biochemical genetic study has shown that triethyl tin may have another mode of action which is related to the transport of Adn nucleotides across the mitochondrial membrane