Impact of studies of the Drosophila norpA mutation on understanding phototransduction.

Studies of the norpA mutation have significantly contributed to understanding the molecular and biochemical basis of phototransduction in Drosophila. Historical milestones in the study of the norpA mutation are reviewed and a contemporary model of the role of the NORPA protein in vision is presented. Questions awaiting further investigations are discussed.

Mutations in cytochrome c oxidase subunit VIa cause neurodegeneration and motor dysfunction in Drosophila.

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.