"Coenzyme Q10 (CoQ10) deficiency is an autosomal recesive disorder where the encephalomyopathy and nephropathy seems to be the most important clinical presentations. Some patients respond to CoQ10 supplementation but others do not. In my Postdoctoral stay in Columbia University I identified the first mutation in PDSS2, which encoded the protein responsible for the syntesis of decaprenyl chain. Moreover, I have studied the pathological consequences associated to CoQ10 deficiency in culture fibroblasts with mutations in PDSS2, COQ2, ADCK3 and COQ9. The results show that mitochondrial bioenergetic, the increase of oxidative stress and the defect in de novo pathway for pyrimidines can be the main pathological mechanisms associated to CoQ10 deficiency. However, the tissue specificity need to be investigated since CoQ10 is present in all cells types and is critical for mitochondrial function. In addition, potential treatment need to be tested. Then, I propose: 1) Generate COQ9 knockin mice. Dra. Rahman’s Group has recently found a mutation in this gene in a patient with CoQ10 deficiency. This gene encode Coq9, an enzyme involved in ubiquinone biosynthesis. However, the function of this enzyme is still unkown and I will study it; 2) Charaterize COQ9 knockin mice including behevioural, clinical, hitological-morphological, physiological, bioquemical and genetical studies; 3) Develop and apply different therapeutical strategies: a) Early an late onset treatment with CoQ10; and b) antioxidant strategy (melatonin administration). The results will be essential to undertand and treat the pathegenesis of CoQ10 deficiency, as well as other primary mitochondrial disorders. Likewise, the results can be important in the treatment of neurodegenerative diseases or aging, since CoQ10 supplementation is been used in clinical trials of parkinson´s patients or it is recommended as nutritional suplemmentation in the elderly population."