Distinct Physiological Functions of Thiol Peroxidase Isoenzymes in Saccharomyces cerevisiae

다국어 초록 (Multilingual Abstract)

A new type of peroxidase("thiol peroxidase"; TPx) having cysteine as the primary site of catalysis has been discovered from prokaryotes to eukaryotes. In addition to two yeast TPx isoforms(TSA Ⅰ and TSA Ⅱ/AHPC1) previously described, three additional TPx-homologues were identified by analysis of the ORF database for Saccharomyces cerevisiae. Three novel isoforms showed a distinct thiol peroxidase activity supported by thioredoxin, and appeared to be distinctively localized in cytoplasm, mitochondria, and nucleus. Each isoform was named after its subcellular localization such as cytoplasmic TPx Ⅰ(cTPx Ⅰ or TSA Ⅰ), cTPx Ⅱ, cTPx Ⅲ(TSA Ⅱ/AHPC1), mitochodrial TPx(mTPx), and nuclear TPx(nTPx). The Northern blot, taken together with the transcriptional activity, suggests that cTPx Ⅰ and cTPx Ⅲ are predominant isoforms acting as principal thiol peroxidase. All types of TPx except for nTPx are inducible in response to oxidative stress. Transcriptional activities of TPx isoenzymes during yeast life span were quite different from each other. Unlike other TPx null mutants, cTPx I null mutant was hypersensitive to various oxidants excluding 4-nitroquinoline N-oxide. The null mutant was more resistant toward 4-nitroquinoline N-oxide than its wild type. Furthermore, deletion of cTPx Ⅰ gave the mutant the power of resistance to acidic culture. The severe growth retardation of cTPx Ⅱ mutant because of the remarkable accumulation of G1-phased cells suggests its possible physiological function as an effecter on cell growth. Based on kinetic properties of five isoforms, their subcellular localizations, and distinct physiology of each null mutant, we discussed the physiological functions of five types of TPx isoenzymes in yeast throughout the full growth cycle.