Humanized yeast to study the role of human ECE-1 isoforms in apoptosis in congenital heart diseases

Abstract

Endothelin convert enzyme-1(ECE-1) plays a significant role in cardiovascular development including four isoforms with unclear function. Therefore, we are interested in studying the function of ECE-1 isoforms through mitochondria due to the high correlation between congenital heart disease (CHD) and apoptosis. Since the expression of human Bax and Bcl-xL in budding yeast (Saccharomyces cerevisiae) results in similar effects in mammalian cells, a yeast system was generated for mimicking human Bax-induced apoptosis and the expression of human ECE-1 isoforms was involved. The correlation between Bax-induced growth defect and the candidates of apoptosis via mitochondrial pathway was preliminarily investigated in this system. Furthermore, the phenotypes of ECE-1 isoforms have been identified through yeast growth defect. Individual ECE-1 isoform does not affect yeast growth but act as enhancers for the Bax-induced growth defect. ECE-1c is the strongest enhancer that affect the expression of candidates of outer membrane translocases. This study indicates that ECE-1 might play an important role in inducing apoptosis and we speculate these findings are possible to provide new perspectives with clarifying the mechanism of CHD.