NUCLEAR-DNA ORIGIN OF CYTOCHROME-C-OXIDASE DEFICIENCY IN LEIGHS SYNDROME - GENETIC-EVIDENCE BASED ON PATIENTS-DERIVED RHO-DEGREES TRANSFORMANTS

Defects of the respiratory chain carrying out oxidative phosphorylation (OXPHOS) are the biochemical hallmark of human mitochondrial disorders. Faulty OXPHOS can be due to mutations in either nuclear or mitochondrial genes, that are involved in the synthesis of individual respiratory subunits or in their post-translational control. The most common mitochondrial disorder of infancy and childhood is Leigh's syndrome, a severe encephalopathy, often associated with a defect of cytochrome c oxidase (COX). In order to demonstrate which genome is primarily involved in COX-deficient (COX(-))-Leigh's syndrome, we generated two lines of transmitochondrial cybrids. The first was obtained by fusing nuclear DNA-less cytoplasts derived from normal fibroblasts, with mitochondrial DNA-less (rho°) transformant fibroblasts derived from a patient with COX(-)-Leigh's syndrome. The second cybrid line was obtained by fusing rho° cells derived from 143B.TK- human osteosarcoma cells, with cytoplasts derived f...