Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System

Abstract

The zebrafish (Danio rerio) is a small vertebrate ideally suited to the modeling of human diseases. Large numbers of genetic alterations have now been modeled and could be used to study organ development by means of a genetic approach. To date, limited attention has been paid to the possible use of the zebrafish toolbox in studying human mitochondrial disorders affecting the nervous system. Here, we review the pertinent scientific literature discussing the use of zebrafish in modeling gene mutations involved in mitochondria-related neurological human diseases. A critical analysis of the literature suggests that the zebrafish not only lends itself to exploration of the pathological consequences of mitochondrial energy output on the nervous system but could also serve as an attractive platform for future drugs in an as yet untreatable category of human disorders.

Keywords: mitochondria; nervous system development; neurodegenerative conditions; zebrafish.

Figure 1

Summary of mitochondria-related genes involved in neurological human disorders, modeled in mutant zebrafish. Mutations in genes involved in mitochondrial electron transport chain, physiology, quality control, dynamics and metabolism, as well as mutations in selected genes encoding carriers and ion channels, can disrupt the integrity of the mitochondrion and/or influence its functions, thus determining the onset of neurological disorders.