Neurologic dysfunction and male infertility in Drosophila porin mutants: a new model for mitochondrial dysfunction and disease

The Journal of Biological Chemistry
Brett H GrahamW J Craigen

Abstract

Voltage-dependent anion channels (VDACs) are a family of small pore-forming proteins of the mitochondrial outer membrane found in all eukaryotes. VDACs play an important role in the regulated flux of metabolites between the cytosolic and mitochondrial compartments, and three distinct mammalian isoforms have been identified. Animal and cell culture experiments suggest that the various isoforms act in disparate roles such as apoptosis, synaptic plasticity, learning, muscle bioenergetics, and reproduction. In Drosophila melanogaster, porin is the ubiquitously expressed VDAC isoform. Through imprecise excision of a P element insertion in the porin locus, a series of hypomorphic alleles have been isolated, and analyses of flies homozygous for these mutant alleles reveal phenotypes remarkably reminiscent of mouse VDAC mutants. These include partial lethality, defects of mitochondrial respiration, abnormal muscle mitochondrial morphology, synaptic dysfunction, and male infertility, which are features often observed in human mitochondrial disorders. Furthermore, the observed synaptic dysfunction at the neuromuscular junction in porin mutants is associated with a paucity of mitochondria in presynaptic termini. The similarity of VDAC mut...Continue Reading

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Related Concepts

Metazoa
Drosophila melanogaster
Respiratory Chain
Subfertility, Male
Mitochondria
Nervous System Disorder
Neurons
Testis
Pore Proteins
Oxidative Phosphorylation Deficiencies

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