Mutations in cytochrome c oxidase subunit VIa cause neurodegeneration and motor dysfunction in Drosophila. Academic Article uri icon

Overview

abstract

  • Mitochondrial dysfunction is involved in many neurodegenerative disorders in humans. Here we report mutations in a gene (designated levy) that codes for subunit VIa of cytochrome c oxidase (COX). The mutations were identified by the phenotype of temperature-induced paralysis and showed the additional phenotypes of decreased COX activity, age-dependent bang-induced paralysis, progressive neurodegeneration, and reduced life span. Germ-line transformation using the levy(+) gene rescued the mutant flies from all phenotypes including neurodegeneration. The data from levy mutants reveal a COX-mediated pathway in Drosophila, disruption of which leads to mitochondrial encephalomyopathic effects including neurodegeneration, motor dysfunction, and premature death. The data present the first case of a mutation in a nuclear-encoded structural subunit of COX that causes mitochondrial encephalomyopathy rather than lethality, whereas several previous attempts to identify such mutations have not been successful. The levy mutants provide a genetic model to understand the mechanisms underlying COX-mediated mitochondrial encephalomyopathies and to explore possible therapeutic interventions.

publication date

  • April 15, 2007

Research

keywords

  • Drosophila
  • Electron Transport Complex IV
  • Motor Activity
  • Nerve Degeneration

Identity

PubMed Central ID

  • PMC1894620

Scopus Document Identifier

  • 34250716562

Digital Object Identifier (DOI)

  • 10.1534/genetics.107.071688

PubMed ID

  • 17435251

Additional Document Info

volume

  • 176

issue

  • 2