Cód. SSPA: IBiS-B-11
Maintenance of a proper redox balance is crucial for survival of all organisms and, consequently, imbalances of redox homeostasis underlay many human pathologies. The thioredoxin and glutathione/glutaredoxin systems are the two main enzymatic systems that regulate redox homeostasis. However, there is still a fundamental lack of knowledge on the molecular mechanisms and pathways by which these two systems control the cellular redox status and their impact in the development of human diseases. Our group employs the model organism Caenorhabditis elegans to gain deeper insight into the molecular function of the thioredoxin and glutathione/glutaredoxin systems, which are highly conserved between worms and humans. For this reason, the findings generated with this preclinical invertebrate model will provide key information that can be transferred into those human diseases for which redox homeostasis unbalance is the primary event.
Research Lines
- Role of glutathione in models of neurodegenerative diseases due to protein aggregation
Our group has described a protective role of reduced glutathione and the enzyme glutathione reductase in C. elegans models of neurodegenerative diseases such as Alzheimer's, Parkinson's or Huntington's. Currently, we are trying to identify and characterize the molecular mechanisms by which glutathione exerts this protective function. Thus, we have found that the protein degradation pathway via autophagy is one of the routes involved, but we have evidence that there could be other additional mechanisms mediated by glutathione, which we intend to elucidate.
- Molecular characterization of ferroptotic cell death
Ferroptosis is a type of cell death that depends on iron and is caused by a massive peroxidation of lipids at the plasma membrane. In this project we aim to demonstrate whether the death that occurs in C. elegans models that express aggregation-prone proteins in muscle cells is due to this type of cell death, which has not yet been characterized in this invertebrate model. We currently have evidence that both the cystine incorporation pathway and the transsulfuration pathway are involved in this mechanism, which we intend to characterize at the genetic and molecular level.
- Implication of a non-canonical pathway of insulin signaling in the maintenance of proteostasis
Signaling by the insulin pathway in mammals is mediated, among others, by a group of proteins called insulin receptor substrate. While these proteins are relatively well characterized in mammals, this is not the case in the C. elegans model. Our group has found evidence that these proteins could be involved in the maintenance of proteostasis by a non-canonical pathway and, therefore, our goal is the functional characterization of this pathway in pathogenic models of protein aggregation.
- Function of the mitochondrial redox systems
Unlike the cytoplasmic thioredoxin and glutathione/glutaredoxin redox systems, the physiological role of the redox systems of the mitochondrial matrix is still poorly understood. We have recently generated a model of C. elegans that lacks the mitochondrial thioredoxin and glutathione/glutaredoxin systems that will help us to identify the functions of these two redox pathways in this organelle.
