1997: D.Phil,Oxford Centre for Molecular Sciences, Oxford University

1997 -2000: Postdoctoral Researcher, Biochemistry Department, Imperial College, London

2000 -2001:Postdoctoral Researcher, Department of Medicine, University College of London

2001 -2003:Postdoctoral Researcher, Biochemistry Department, Manchester University

2003 - 2011: The Royal Society University Research Fellow, Faculty of Life Sciences, Manchester University

2011 – Lecturer of Biochemistry, Faculty of Life Sciences, Manchester University

Research interests


Mitochondria are vitally important organelles of eukaryotic cells, which perform essential functions in all important biological processes, from ATP generation to cell growth and cell death (apoptosis). Mitochondrial dysfunction leads to life threatening diseases, including diabetes, stroke, cancer, and neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases). Majorities of mitochondrial proteins (~99%) are synthesized in the cytosol and thus import of the proteins into the organelle is essential for biogenesis of mitochondria. We are interested in development and application of a wide range of methods to understand the molecular mechanisms of mitochondrial protein import, as well as folding and function of key proteins involved in the process.

Biogenesis, Folding and Function of Mitochondrial Proteins

Mitochondrial biogenesis depends on import proteins from the cytosol, since the majority of mitochondrial proteins are synthesized in the cytosol and have to be imported into mitochondria for function. We are particularly interested in understanding how the mitochondrial intermembrane space (IMS) proteins are imported into the IMS, and how they are folded and maintained in an active state.  Studies showed that most of the IMS proteins are imported into mitochondria via the redox-regulated MIA (mitochondrial import and assembly) pathway. Our previous research focused on the molecular mechanisms of the import of and functions of the mitochondrial IMS proteins. We showed that thiol-disulphide redox regulation plays a key role during the biogenesis and function of the mitochondrial IMS proteins (Lu et al 2004 J Biol Chem; Morgan & Lu 2008 Biochem J, Ang & Lu 2009 J Biol Chem, Ang et al. 2014 Biochem J, Ceh-Pavia et al 2014 Biochem J). Cys-reduced proteins can be imported into mitochondria, but oxidized (disulphide bounded) precursor proteins are folded and thus cannot be imported into mitochondria. Whilst the newly imported proteins are oxidised inside mitochondria in a process catalysed by the MIA machinery, they are kept in reduced forms in the cytosol and facilitated by the cytosolic redoxin systems (Durigon et al. 2012 EMBO rep). Our current interests are the mechanisms of folding and quality control of the IMS proteins and their role in disease.

Mechanism of the MIA machinery and its role in disease

The MIA machinery contains two essential proteins: the oxidoreductase Mia40 and the FAD-dependent sulfhydryl oxidase Erv1/ALR (called Erv1 in yeast, ALR in human). Despite a wealthy knowledge on the structure and functional mechanism of Mia40-Erv1 system has been established, a littler is known about the biogenesis and maturation of Erv1/ALR. Apart from function in the MIA pathway, Erv1/ALR also functions in different cellular and physiological processes, for which the molecular mechanisms are unknown. We are aiming to address these issues by investigating the correlation between import, folding, oligomerisation and function of the proteins. Moreover, flavoprotein oxidases have been widely employed in biocatalytic processes. Thus, understanding the folding and cofactor binding of Erv1/ALR is not only crucial for understanding the molecular mechanisms of the proteins in normal biological processes and diseases, but also important for design novel flavoproteins for biocatalytic industry.

Mechanisms of protein quality control in the mitochondrial IMS

The small Tim proteins of the mitochondrial IMS are novel ATP-independent chaperones. They play an essential role during the biogenesis of mitochondrial membrane proteins, by preventing the hydrophobic proteins from aggregating in the aqueous environment of the IMS. Although crystal structure of the small Tim protein complexes have been determined, little is known how these novel chaperones mediate the import of their substrate proteins, and how they are maintained in a functional form. Thus we also interested in understanding the functional mechanism of the small Tim proteins.  On the other hand, studies showed that misfolding and mutation can induce clearance of the small Tim proteins by the mitochondrial i-AAA protease, Yme1. Using the small Tim proteins and Yme1 as models, we are investigating the mechanisms of protein quality control and homeostasis of the mitochondrial IMS proteins.


We are addressing these questions using a range of biological, biochemical and biophysical techniques. Such as molecular biology, mitochondrial protein import, protein purification, thiol-modification, electrophoresis, chromatography, and various spectroscopic methods, as well as stopped-flow kinetics techniques.  We aim to elucidate molecular mechanisms of the proteins in health and disease comprehensively.

Research profile


2nd Year Course: BIOL21111 Proteins

2nd year Biochemistry RSM

1st/2nd Year Biochemistry Tutorials

Final Year Biology Tutorial

2nd Year Dissertation Students

Final Year Project Students

Erasmus Exchange Students

MSc Research Project

Biosciences International Summer School (BIO-SISS)

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