Biogenesis and functional mechanism of mitochondrial sulfhydryl oxidase proteins in health and disease

Mitochondrial sulfhydryl oxidases Erv1/ALR play an essential role in biogenesis of mitochondria – the power plant of eukaryotic cells. They are essential components of the mitochondrial import and assembly (MIA) pathways, which catalyse the import and oxidative folding of many mitochondrial proteins. Both Erv1 (in yeast) and ALR (in human) are flavoproteins using FAD as a cofactor for their function. Flavoproteins are an important group of proteins; they have been widely employed in bio-catalytic processes. Moreover, a surprisingly large number of flavoproteins have been reported to be associated with diseases caused by mutations, such as the autosomal recessive myopathy caused by a single mutation in human ALR (R194H). Although structure and functional mechanism of the key components of the MIA import pathway has been well studied in recent years, many questions about the biogenesis and function of the Erv1/ALR enzymes are still remain to be answered. We still lack of knowledge on how Erv1/ALR are imported into mitochondria and how the maturation occurred in mitochondria.

This PhD project will focus on investigating the function, folding and cofactor assembly mechanisms of the wild-type and diseases associated mutant Erv1. A wide range of biochemical and biophysical methods, such as protein purification, enzyme activity assay, mitochondrial import, spectroscopic techniques (UV-vis absorption, circular dichroism, fluorescence), and stopped-flow kinetic analyses will be used to address the biogenesis and functional mechanisms of Erv1/ALR in health and disease. An enthusiastic student with a good background in Biochemistry and relevant subjects is required. The student will get training and have opportunity to learn most of the techniques during this PhD project.