Nuclear DNA origin of cytochrome c oxidase deficiency in Leigh's syndrome: Genetic evidence based on patient's-derived rho○ transformants

Valeria Tiranti, Monica Munaro, Doriana Sandonà, Eleonora Lamantea, Marco Rimoldi, Stefano DiDonato, Roberto Bisson, Massimo Zeviani

Research output: Contribution to journalArticlepeer-review


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 posttranslational 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 from the same patient. The first cybrid line showed a specific and severe COX(-) phenotype, while in the second all the respiratory chain complexes, including COX, were normal. These results indicate that the COX defect in our patient is due to a mutation of a nuclear gene. The use of cybrids obtained from 'customized', patient-derived rho cells can have wide applications in the identification of respiratory chain defects originated by nuclear DNA-encoded mutations, and in the study of nuclear DNA-mitochondrial DNA interactions.

Original languageEnglish
Pages (from-to)2017-2023
Number of pages7
JournalHuman Molecular Genetics
Issue number11
Publication statusPublished - Nov 1995

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)


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