Mitochondrial Medicine and Biology

Mitochondria play a fundamental role in cell and energy metabolism and consequently mitochondrial dysfunction can lead to severe multi-system disorders with wide range of clinical presentations that commonly include neurodegeneration, muscle defects and exercise intolerance. To understand these conditions better and identify therapeutic targets it is necessary to understand how gene expression is regulated within mitochondria as some of the most significant gaps in our knowledge of mitochondrial function and disease are in the regulation of mitochondrial gene expression. Links between transcription and translation in mammalian mitochondria are not known. Mitochondrial mRNAs are transcribed as part of long primary transcripts that generally encompass the entire mtDNA, therefore the ratios of the 13 mammalian mitochondrial mRNAs and their proteins must be controlled at a post-transcriptional level. Little is known about how these 13 mRNAs are regulated in mammalian mitochondria. This is particularly important since tissue-, cell- and disease-specific variations in expression of the 13 different mtRNAs has been observed, but cannot be explained at present. The basic components and mechanisms of transcription have recently been discovered, however the control of mRNA processing, translation and stability remains unknown.

Senior Research Staff

Dr Aleksandra Filipovska Head, Mitochondrial Medicine and Biology Research: mitochondrial RNA-binding proteins, mitochondrial gene expression, mitochondrial translation, mitochondrial dysfunction in disease

Research Details

Mitochondrial RNA-binding proteins

We are interested in identifying mammalian mitochondrial RNA-binding proteins and investigating their role in RNA metabolism in cells. Discovery of proteins and the RNAs they bind may shed light on the regulation of gene expression in mammalian mitochondria. In addition, we are developing new methods for the identification of mitochondrial RNAs bound by the mitochondrial RNA-binding proteins that may regulate their expression in health and in disease.

Mitochondria as targets for chemotherapeutics

Recent developments in understanding the central place of mitochondria as a regulator of cell death have stimulated enormous interest in targeting mitochondria in new approaches to cancer chemotherapy. A major aim for this research is to overcome the two problems in cancer chemotherapy, drug resistance and the lack of selectivity of cancer drugs in differentiating between normal and tumour cells. A number of therapeutic strategies targeting mitochondria for cancer therapy have been described which include a variety of gold compounds. We are investigating the mechanism of selective antitumour activity of gold lipophilic compounds in cancer cells, which will enable us to identify gold compounds with optimal properties that selectively target mitochondrial antioxidant proteins in cancer cells. The aim is to develop novel and unique probes for the study of mitochondrial redox regulation in cells and aid the development of new chemotherapeutics.