A novel mtDNA mutation in the ATPase6 gene studied by E. coli modeling

R Carrozzo; J Murray; O Capuano; A Tessa; G Chichierchia; M R Neglia; R A Capaldi; F M Santorelli

doi:10.1007/s100720070016

A novel mtDNA mutation in the ATPase6 gene studied by E. coli modeling

Neurol Sci. 2000;21(5 Suppl):S983-4. doi: 10.1007/s100720070016.

Authors

R Carrozzo¹, J Murray, O Capuano, A Tessa, G Chichierchia, M R Neglia, R A Capaldi, F M Santorelli

Affiliation

¹ Department of Molecular Medicine and Neurology, IRCCS Bambino Gesù, I-00165 Rome, Italy.

PMID: 11382202
DOI: 10.1007/s100720070016

Abstract

This study aimed to understand the pathogenesis of a new mtDNA-related etiology of Leigh syndrome. We identified the T9176G mutation as the molecular basis of Leigh syndrome in a child and looked for alterations in cellular ATP production. We then modeled the new mtDNA mutation in E. coli and analyzed ATP synthesis, hydrolysis, and the ability of the mutated enzyme to pump protons. Our results suggest that the T9176G change results in a novel, fully assembled enzyme which inhibits the holoenzyme probably by blocking the proton pathway.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / genetics*
Adenosine Triphosphatases / metabolism
Adenosine Triphosphate / biosynthesis*
Adenosine Triphosphate / genetics*
Brain / enzymology
Brain / pathology
Brain / physiopathology
Child
Child, Preschool
DNA Mutational Analysis
DNA, Mitochondrial / genetics*
Electron Transport / genetics
Escherichia coli / genetics*
Female
Genes / genetics
Humans
Leigh Disease / enzymology
Leigh Disease / genetics*
Leigh Disease / physiopathology
Models, Genetic
Point Mutation / genetics*
Protein Structure, Tertiary / genetics

Substances

DNA, Mitochondrial
Adenosine Triphosphate
Adenosine Triphosphatases