Disease relevance of ATH1

• Characterization of the treA gene encoding this trehalase shows that it is homologous to Saccharomyces cerevisiae vacuolar acid trehalase, the product of the ATH1 gene, and to two related proteins of unknown function identified in Mycobacterium tuberculosis and Mycobacterium leprae [1].
• Disruption of the yeast ATH1 gene confers better survival after dehydration, freezing, and ethanol shock: potential commercial applications [2].

High impact information on ATH1

• After screening a Candida albicans genome data base, the product of an open reading frame (IPF 19760/CA2574) with 41% identity to Saccharomyces cerevisiae vacuolar acid trehalase (Ath1p) was identified and named Atc1p [3].
• By using an adaptation of the assay of invertase on whole cells with NaF, we showed that more than 90% of the activity of Ath1p is extracellular, splitting of the disaccharide into glucose [4].
• However, the molecular mechanism by which extracellular trehalose can be transported to the vacuole and degraded by the acid trehalase Ath1p is not clear [4].
• To retain the accumulation of trehalose in yeast cells, we constructed, for the first time, diploid homozygous neutral trehalase mutants (Deltanth1), acid trehalase mutants (Deltaath1), and double mutants (Deltanth1 ath1) by using commercial baker's yeast strains as the parent strains and the gene disruption method [5].
• Yeast strains disrupted for ATH1, which encodes vacuolar acid trehalase, have been reported to grow to higher cell densities than reference strains [6].

Chemical compound and disease context of ATH1

• In addition, the elevated levels of trehalose in the delta ath1 strain correlated with increased tolerance to dehydration, freezing, and toxic levels of ethanol [2].

Biological context of ATH1

• Experiments with diploid strains heterozygous for delta ath1 show a gene dosage effect for the ATH1 gene for growth on trehalose [7].
• We have analyzed the role of the acid trehalase in trehalose hydrolysis using the ATH1 deletion mutant (delta ath1) of Saccharomyces cerevisiae [M [7].
• The role of trehalose as cell protector against oxidative stress induced by H(2)O(2) has been studied in Saccharomyces cerevisiae mutants in which the two trehalase genes ATH1 and NTH1 are deleted [8].
• Our results show that the vacuolar acid trehalase Ath1p is necessary for the phenotype of growth on trehalose, i.e. trehalose utilization, in contrast to cytosolic neutral trehalase Nth1p which is necessary for intracellular degradation of trehalose [7].
• We have isolated a plasmid containing a gene, ATH1, that results in eight- to ten-fold higher acid trehalase activity in yeast cells when present in high copy [9].

Associations of ATH1 with chemical compounds

• Deletion of the ATH1 gene in Saccharomyces cerevisiae prevents growth on trehalose [7].
• Elevated growth of Saccharomyces cerevisiae ATH1 null mutants on glucose is an artifact of nonmatching auxotrophies of mutant and reference strains [6].
• Antisense-mediated inhibition of acid trehalase (ATH1) gene expression promotes ethanol fermentation and tolerance in Saccharomyces cerevisiae [10].

Analytical, diagnostic and therapeutic context of ATH1

• In conclusion, disruption of ATH1 by genetic engineering apparently does not promote the survival of viable cells and DNA in natural environments [11].

References