Research groups

Cell biology and Biotechnology

Dr Plácido Navas Lloret. UPO
Control of oxidative stress
Dr Plácido Navas Lloret. UPO
Principal Investigator

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Coenzyme Q (ubiquinone, CoQ) is a lipid with redox functions and a highly conserved structure in evolution. It is required for the development of respiration. It also functions as antioxidant in those membranes where it is present. CoQ is reduced by both mitochondrial reductases and plasma membrane dehydrogenases, where it is a component of a highly regulated antioxidant complex. The regulation of CoQ biosynthesis is a very complex process and not much known. This biosynthesis involves genes with a high conserved homology among species. The deletion of any of these genes in strictly aerobic organisms is lethal and individuals harboring mutations in these genes show either defects in development or pleiotropic effects in adulthood. The object of our work is to determine the mechanisms that regulate CoQ biosynthesis and the possible modifications in human fibroblasts isolated from ataxic patients showing a primary deficiency of CoQ. We use C. elegans and cultured human cells as research models. We have demonstrated by RNAi the participation of eight genes (coq1 to coq8) in CoQ biosynthesis in C. elegans. We have cloned these genes and have generated nematode stable strains harboring a construction that includes the sequence of one coq gene, the sequence of the endogenous promoter, and the sequence of GFP. We will use these strains to study the expression pattern of these genes throughout nematode life, especially in aging and early development. We have detected a primary deficiency of CoQ in fibroblasts isolated from ataxic patients and we are studying the functional complementation of cloned from these cells to determine the cause of deficiency. Further, we are working in the hypothesis that the nuclear activation of caspase3 can induce an increase of mitochondrial CoQ biosynthesis as a mechanism of cellular survival.