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Title: Biochemical and molecular genetic studies on mitochondrial ATPase
Author: Connerton, Ian
ISNI:       0000 0001 3561 289X
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1986
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An attempt has been made to rationalise the multi-faceted inhibitory actions of trialkyltins on mitochondria, including studies on their inhibition of ATP synthase and concomitant depolarisation of mitochondrial membrane potential in rat liver mitochondria. These functions have been shown to occur in the absence of halide/hydroxyl exchange. The majority of trialkyltin compounds studied here show a concentration dependent differential inhibition of the ATP hydrolase and ATP synthase functions of the mitochondrial ATPase complex. The relative trialkyltin concentrations at which these events take place, are in the order of ATPase >ATP synthase ^p reduction. A comparison has been made between the n-alkyltins and internally penta-coordinated alkyl tins, revealing penta-coordinacy per se does not give rise to potent inhibitory action. However, the infernally nitrogen-tin coordinated species (2- (dimethylamino) methyl diethyltin halide, provides an excellent specific inhibitor of the mitochondrial ATPase complex. The relative sensitivities to the mitochondrial ATPase directed drugs, oligomycin and ossamycin, of wild type and drug specific mutants of the yeast Saccharomyces cerevisiae has been assessed both in vivo and in vitro. DNA sequencing studies of mutant and wild type mitochondrial DNAs have established the localisation of the mutant alleles 01 iR2-76 and 0ss"l-92, and their respective predicted aminoacid residue changes: methionine to phenylalanine and aspartic acid to asparagine, in subunit 6 of the OS-ATPase complex. Wild type DNA sequence has also revealed the genes for subunit 8 of OS-ATPase and a putative maturase sequence, downstream of the 0li 2 gene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QC Physics ; QP Physiology