University of Leicester
2022XIEHPHD.pdf (5.8 MB)

Investigating the Potential Roles of Human (Endothelin convert enzyme-1) ECE-1 in Congenital Heart Diseases Using a Humanized Yeast System of Apoptosis

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posted on 2022-06-17, 13:14 authored by Hanhui Xie

CHDs (congenital heart diseases) are the most common birth defects that affects over 1% of new-borns and there are approximately 30-50% of mortality caused by birth defects is due to the occurrence of CHDs in the world, however, CHD is a complex disease, the prognosis of CHDs is not optimistic. Therefore, it is critical to explore the mechanism of CHDs and new strategy of treatment is urgently needed.

ECE-1 (Endothelin convert enzyme-1) plays a significant role in cardiovascular development and cardiac defects. ECE-1 has four isoforms that are located at different position in the cell, however, the function of four isoforms remains unclear. Therefore, we are interested in studying whether the four isoforms have different function in inducing apoptosis through mitochondria due to the high correlation between CHDs and apoptosis.

The B cell lymphoma 2 (Bcl-2) family consists of a number of pro-apoptotic members (e.g., Bax) and anti-apoptotic members (e.g., Bcl-xL), which regulate apoptosis by activating mitochondrial events. The heterologous expression of human Bax and Bcl-xL in budding yeast (Saccharomyces cerevisiae) resulted in similar effects to those in mammalian cells.

In this study, a humanized yeast system has been generated for mimicking human Bax-induced apoptosis and the heterologous expression of human ECE-1 isoforms was involved. Based on this system, the potential relationship between Bax-induced growth defect and several important mitochondrial genes was preliminarily investigated. Furthermore, the phenotypes of ECE-1 isoforms have been identified by analyzing the growth defect of yeast cells. ECE-1c was the most powerful enhancer for Bax-induced growth defect, the function of which is be able to affect the expression of mitochondrial genes related to outer membrane translocases. These findings indicated that ECE-1 might play an important role in inducing apoptosis and new perspectives for further clarifying the mechanism, prediction or therapy of CHDs.



Ed Louis; Sandra Beleza

Date of award


Author affiliation

Department of Genetics and Genome Biology

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD