Cell Death Regulation

Programme Leader: L. Miguel Martins

Summary of Research Interests

The focus of our research is to better understand the control of cellular death processes in normal cells as well as in pathological states where alterations of these processes have occurred. Our aim is to achieve a better understanding of the regulatory mechanisms controlling cell death. Understanding the basic biology of these processes can provide insights that might lead to targeted treatment solutions that will act on pathways and alter disease at its cause resulting in a better type of medicine.

Part of our research addresses the function of mitochondrial proteins HtrA2 and PINK1 and their role in stress responses. Mutations in HtrA2 and PINK1 have been linked to Parkinson’s disease. We have recently identified a mitochondrial stress-sensing pathway that involves the interaction between these two proteins.

Currently our work focuses on identifying mitochondrial signaling pathways whose function involves the suppression of cellular stress. The aim of this work is to target these to improve neuronal health in models of Parkinson’s disease as well as other diseases related to mitochondrial dysfunction (see illustration below).

Our research in the  news:

Interview by ITV Central, a UK TV channel concerning our latest work on metabolic stress pathways. Click here for a link.

Article in the Science section of Público by Ana Gerschenfeld. Público is a high circulation portuguese broadsheet newspaper. This covers our latest work on folic acid as an agent to suppress neurodegeneration in flies. Click here for a link.

Article in BioWorld by Sharon Kingman. This focuses on our recent work focusing on nucleotide metabolism. Click here for a link.

An article in the “research highlights” section of Nature Chemical Biology explaining our recent findings, linking nucleotide salvage pathways and neurodegeneration. Click here for a link.

 

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Selected recent research publications:

Tufi, R. et al. Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson’s disease. Nature Cell Biology  (2014), Pubmed

Moisoi, N. et al. Loss of PINK1 enhances neurodegeneration in a mouse model of Parkinson’s disease triggered by mitochondrial stress. Neuropharmacology (2013), Pubmed

de Castro, I. P. et al. Drosophila ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants. Cell Death and Disease (2013), Pubmed

Costa, A.C. et al. Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/Parkin model of Parkinson’s disease. Cell Death and Disease (2013), Pubmed

de Castro, I. et al. Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster. Cell Death and Differentiation (2012), Pubmed

Selected recent review articles:

Celardo, I., Martins, L.M., Gandhi, S. Unravelling mitochondrial pathways to Parkinson’s disease. British Journal of Pharmacology (2013), PubMed

Lehmann, S. and  Martins, L. M. Insights into mitochondrial quality control pathways and Parkinson’s disease. J. Mol. Med. (2013), PubMed