Adenylate kinase 2 deficiency limits survival and regulates various genes during larval stages of Drosophila melanogaster

Adenylate kinase isozyme 2 (AK2) is located in mitochondrial intermembrane
space and regulates energy metabolism by reversibly converting ATP and AMP to 2 ADPs.
We previously demonstrated that disruption of the Drosophila melanogaster AK2 gene
(Dak2) resulted in growth arrest during the larval stage and subsequent death. Two other
groups found that human AK2 mutations cause reticular dysgenesis, a form of severe combined
immunodeficiency (SCID) that is associated with severe hematopoietic defects and
sensorineural deafness. However, the mechanisms underlying differential outcomes of AK2
deficiency in Drosophila and human systems remain unknown. In this study, effects of
tissue-specific inactivation of the Dak2 gene on Drosophila development were analyzed
using RNAi-mediated gene knockdown. In addition, to investigate the roles of AK2 in the
regulation of gene expression during development, microarray analysis was performed using
RNA from first and second instar larvae of Dak2-deficient mutant and wild-type D.
melanogaster. Knockdown of Dak2 in all germ layers caused cessation of growth and subsequent
death of flies. Microarray analysis revealed that Dak2 deficiency downregulates
various genes, particularly those involved in the proteasomal function and in mitochondrial
translation machinery. These data indicate that adenine nucleotide interconversion by
Dak2 is crucial for developmental processes of Drosophila melanogaster.