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 journalArticle

7 Citations (Scopus)

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

Fingerprint

Leigh Disease
Adenosine Triphosphatases
Protons
Adenosine Triphosphate
Escherichia coli
Mutation
Neurologic Gait Disorders
Oxidative Phosphorylation
Electron Transport
Site-Directed Mutagenesis
Mitochondrial DNA
DNA Sequence Analysis
Genes
Autopsy
Mitochondria
Skeletal Muscle
Seizures
Animal Models
Fibroblasts
Biopsy

Keywords

  • ATPase 6
  • Escherichia coli
  • Leigh syndrome
  • mtDNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

@article{21100f707be74d6f8787e8d902ec63b9,
title = "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",
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.",
keywords = "ATPase 6, Escherichia coli, Leigh syndrome, mtDNA",
author = "R. Carrozzo and T. Rizza and S. Lucioli and R. Pierini and E. Bertini and Santorelli, {F. M.}",
year = "2004",
month = "5",
language = "English",
volume = "93",
pages = "65--67",
journal = "Acta Paediatrica, International Journal of Paediatrics, Supplement",
issn = "0803-5326",
publisher = "Taylor and Francis Ltd.",
number = "445",

}

TY - JOUR

T1 - 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

AU - Carrozzo, R.

AU - Rizza, T.

AU - Lucioli, S.

AU - Pierini, R.

AU - Bertini, E.

AU - Santorelli, F. M.

PY - 2004/5

Y1 - 2004/5

N2 - 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.

AB - 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.

KW - ATPase 6

KW - Escherichia coli

KW - Leigh syndrome

KW - mtDNA

UR - http://www.scopus.com/inward/record.url?scp=2342620052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342620052&partnerID=8YFLogxK

M3 - Article

VL - 93

SP - 65

EP - 67

JO - Acta Paediatrica, International Journal of Paediatrics, Supplement

JF - Acta Paediatrica, International Journal of Paediatrics, Supplement

SN - 0803-5326

IS - 445

ER -