Glutamate dehydrogenases are enzymes that take part in both amino acid and energy
metabolism. Their role is clear in many biological processes, from neuronal function
to cancer development. The putative testis-specific Drosophila glutamate dehydrogenase,
Bb8, is required for male fertility and the development of mitochondrial derivatives
in spermatids. Testis-specific genes are less conserved and could gain new functions,
thus raising a question whether Bb8 has retained its original enzymatic activity.
We show that while Bb8 displays glutamate dehydrogenase activity, there are significant
functional differences between the housekeeping Gdh and the testis-specific Bb8. Both
human GLUD1 and GLUD2 can rescue the bb8 ms mutant phenotype, with superior performance
by GLUD2. We also tested the role of three conserved amino acids observed in both
Bb8 and GLUD2 in Gdh mutants, which showed their importance in the glutamate dehydrogenase
function. The findings of our study indicate that Drosophila Bb8 and human GLUD2 could
be novel examples of convergent molecular evolution. Furthermore, we investigated
the importance of glutamate levels in mitochondrial homeostasis during spermatogenesis
by ectopic expression of the mitochondrial glutamate transporter Aralar1, which caused
mitochondrial abnormalities in fly spermatids. The data presented in our study offer
evidence supporting the significant involvement of glutamate metabolism in sperm development.
