CNR Personell: Annamaria Tonazzi, Roberto Arrigoni, Nicola Giangregorio, Massimo Lasorsa, Eleonora Paradies, Riccardo Merafina
Research Associate: Cesare Indiveri, Ferdinando Palmieri, Luigi Palmieri
SV.P14.007 “Mitochondrial carriers: structure and functional mechanisms” is involved in the identification and in the functional and structural characterization of mitochondrial membrane transporters belonging to the family SLC25 known as “mitochondrial carrier family (MCF)”. In humans, 53 genes encode proteins of the SLC25 family and each of them translocates specific metabolites across the inner mitochondrial membrane, allowing the integration and completion of important metabolic processes that take place between mitochondria and cytosol.
a) Study of the relationship between structure and function of mitochondrial carriers using site-directed mutagenesis, chemical modification, reconstitution and homology modeling. Effects of either endogenous and xenobiotic molecules on the transport activity, mediated by mitochondrial carriers.
b) Identification of the catalytic activity of members of the mitochondrial carrier family with still unknown function, and study of their physiological role in cellular models as well as in vitro.
c) Identification of mutations of genes encoding members of the SLC25 family in patients suffering diseases associated with dysfunction of mitochondrial carriers and study of pathogenetic mechanisms in cell models.
Cellular systems and model organisms
a) Use both in vitro systems such as proteoliposomes that are reconstituted with animal proteins (man, rat, zebrafish) or fungi (A. nidulans), and in vivo systems such as primary cells as rat sensory-neurons and cell lines: Hela , HepG2, ChoK1.
b) Functional identification and reconstitution of recombinant SLC25 proteins of different species (mammals, C. elegans, D. melanogaster, yeast) in proteoliposomes.
c) Study of the physiological role and of pathogenetic mechanisms of SLC25 proteins using experimental approaches such as overexpression and gene silencing in cell models: yeast (S. cerevisiae) or in primary and secondary mammalian cell lines.
The primary objective is to increase the knowledge of the mechanisms underlying the transport of metabolites across biological membranes, in particular mitochondrial carriers, using both classical and innovative experimental approaches and technologies. Several experimental models have been developed and used to study the cellular metabolism and the regulation of gene expression of mitochondrial proteins.
Metabolic role of Carrier Mitocondriali