A mitochondrial ATPase 6 mutation is associated with Leigh syndrome in a family and affects proton flow and adenosine triphosphate output when modeled in Escherichia coli

R. Carrozzo, T. Rizza, S. Lucioli, R. Pierini, E. Bertini, F. M. Santorelli

Research output: Contribution to journalArticlepeer-review

Abstract

A multidisciplinary strategy was used to identify the molecular defect in a family with Leigh syndrome (LS). The propositus presented severe developmental delay, an ataxic-spastic gait and seizures. She died at 3.5 y of age from cardiorespiratory arrest. Postmortem examination disclosed pathological features typical of LS. A 12-y-old sister is affected with the same disease. Respiratory chain enzyme complex activities in skeletal muscle biopsy were normal. Adenosine triphosphate (ATP) synthesis during oxidative phosphorylation in skin fibroblasts mitochondria showed a severely hampered ATP production. Mitochondrial DNA sequencing revealed a new mutation in the ATPase 6 gene (T9176G). Site-directed mutagenesis in Escherichia coli strains was used to measure H+ pumping and ATP synthesis. Results were comparable to findings obtained in human cells. These data corroborate the use of E. coli strains as a feasible "animal" model for functional studies in pathogenic mutations of the ATPase 6 gene.

Original languageEnglish
Pages (from-to)65-67
Number of pages3
JournalActa Paediatrica, International Journal of Paediatrics, Supplement
Volume93
Issue number445
Publication statusPublished - May 2004

Keywords

  • ATPase 6
  • Escherichia coli
  • Leigh syndrome
  • mtDNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint Dive into the research topics of 'A mitochondrial ATPase 6 mutation is associated with Leigh syndrome in a family and affects proton flow and adenosine triphosphate output when modeled in Escherichia coli'. Together they form a unique fingerprint.

Cite this