Misregulation of bromotyrosine compromises fertility in male <i>Drosophila</i>.

Abstract

Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during <i>Drosophila</i> spermatogenesis. Bromotyrosine is not evident when <i>Drosophila</i> express a native flavin-dependent dehalogenase that is homologous to the enzyme responsible for iodide salvage from iodotyrosine in mammals. Deletion or suppression of the dehalogenase-encoding condet (<i>cdt</i>) gene in <i>Drosophila</i> allows bromotyrosine to accumulate with no detectable chloro- or iodotyrosine. The presence of bromotyrosine in the <i>cdt</i> mutant males disrupts sperm individualization and results in decreased fertility. Transgenic expression of the <i>cdt</i> gene in late-staged germ cells rescues this defect and enhances tolerance of male flies to bromotyrosine. These results are consistent with reversible halogenation affecting <i>Drosophila</i> spermatogenesis in a process that had previously eluded metabolomic, proteomic, and genomic analyses.