Cellular reduction/oxidation (redox status) regulates various aspects of cellular functions such as proliferation, activation, growth inhibition and cell death. Biological systems are continuously exposed to oxidants that can be either generated endogenously by metabolic reactions (e.g. from mitochondrial electron transport during respiration or during activation of phagocytes) or exogenously. To protect against exposure to oxidants, the cells have a well-developed antioxidant system that includes both enzymatic (e.g thioredoxin, superoxide dismutase, catalase glutathione peroxidase) and nonenzymatic (glutathione) systems. An imbalance occurs between oxidants and antioxidants, in favour of oxidants (oxidative stress) has been directly linked to oxidation of proteins DNA and lipids, which may induce a variety of cellular responses through the generation of secondary metabolic reactive oxygen species.

Thioredoxins (Trx) are a class of small 12-kDa redox proteins known to be present in all eukaryotic and prokaryotic organisms. They are characterized by a highly conserved active site that contains two cysteine residues which are reduced from the oxidized form by the flavoenzyme thioredoxin reductase (TrxR) and NADPH [the thioredoxin system]. Mammalian thioredoxin has a variety of biological activities. It was originally studied for its ability to act as hydrogen donor for ribonucleotide reductase, the enzyme that synthesizes deoxyribonucleoside triphosphates for DNA synthesis. It can also serve as a cofactor for methionine sulfoxide reductase, catalyze reduction of protein disulfide bonds and participate in folding of proteins. Thioredoxin can also modulate the DNA binding activity of receptors and transcription factors. Furthermore, thioredoxin can scavenge free radicals and is able to protect cells against oxidative stress.

Mammalian cells were long thought to contain only one form of Trx located in the cytosol which, under certain conditions, could be translocated to the nucleus. Since 1996, our group has been engaged in the search of novel members of the thioredoxin family of proteins. This has resulted in the identification of a mitochondrial thioredoxin system (Trx2 and TrxR2), a ubiquitous thioredoxin-like protein of unknown function (Txl), two tissue-specific member of the family in human spermatozoa, Sptrx-1 and Sptrx-2. We have more recently characterized two novel members: ERdj5, present in the endoplasmic reticulum and Txl-2, expressed in ciliated cells.

Ongoing projects in our laboratory include
1. The characterisation of the novel chaperone ERdj5
2. The characterisation of Mitochondrial Thioredoxin Reductase
3. The characterisation of Mitochondrial Thioredoxin 2
4. Studying the interactions between redox systems and estrogen receptors

Current group members:
• Giannis Spyrou, PhD, Associate Professor, Group Leader
• Tassos Damdimopoulos, PhD.
• Paula Cunnea, BSc, PhD student
• Ivan Nalvarte, PhD student

Previous group members:
• Alberto Jiménez Garcia, PhD (now at Dept of Microbiology and Genetics, Salamanca University, Salamanca, Spain)
• Antonio Miranda Vizuete, PhD (now at Dept of Developmental Biology, Pablo de Olavide (UPO) University, Seville, Spain)