SCULLY, AN ESSENTIAL GENE OF DROSOPHILA, IS HOMOLOGOUS TO MAMMALIAN MITOCHONDRIAL TYPE-II L-3-HYDROXYACYL-COA DEHYDROGENASE AMYLOID-BETA PEPTIDE-BINDING PROTEIN

The characterization of scully, an essential gene of Drosophila with p henocritical phases at embryonic and pupal stages, shows its extensive homology with vertebrate type II L-3-hydroxyacyl-CoA dehydrogenase/ER AB. Genomic rescue demonstrates that four different lethal mutations a re scu alleles, the molecular nature of which has been established. On e of them, scu(3127), generates a nonfunctional truncated product. scu (4058) also produces a truncated protein, but it contains most of the known functional domains of the enzyme. The other two mutations, scu(1 74) and scu(S152), correspond to single amino acid changes. The expres sion of scully mRNA is general to many tissues including the CNS; howe ver, it is highest in both embryonic gonadal primordia and mature ovar ies and testes. Consistent with this pattern, the phenotypic analysis suggests a role for scully in germ line formation: mutant testis are r educed in size and devoid of maturing sperm, and mutant ovarioles are not able to produce viable eggs. Ultrastructural analysis of mutant sp ermatocytes reveals the presence of cytoplasmic lipid inclusions and s carce mitochondria. In addition, mutant photoreceptors con tain morpho logically aberrant mitochondria and large multilayered accumulations o f membranous material, Some of these phenotypes are very similar to th ose present in human pathologies caused by beta-Oxidation disorders.