title: Drosophila delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is required for proline breakdown and mitochondrial integrity-Establishing a fly model for human type II hyperprolinemia.
abstract: Delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is a nuclear-encoded mitochondrial enzyme that catalyzes the second step in proline degradation. Mutations in human P5CDh cause type II hyperprolinemia, a complex syndrome displaying increased serum proline and mental disabilities. Conceptual gene CG7145 in Drosophila melanogaster encodes the orthologous DmP5CDh1. The mutant allele CG7145(f04633) contains a piggyBac transposon that truncates the enzyme by 83 residues. Heterozygous (CG7145(f04633)/TM3) individuals developed normally, while homozygous (CG7145(f04633)/CG7145(f04633)) individuals displayed proline levels twice that of normal, swollen mitochondria, and ultimately larval and pupal lethality. We believe this is the first correlation between the loss of P5CDh and morphological defects in mitochondria.
authors.affiliation: Department of Biological Sciences, 202 Life Sciences Building, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: DiMario
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000235:genetics / Q000378:metabolism* / Q000172:deficiency; D000592:Amino Acid Metabolism, Inborn Errors / Q000473:pathology; D000818:Animals; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011392:Proline / Q000378:metabolism*; D011394:Proline Oxidase / Q000172:deficiency; D017384:Sequence Deletion; D016019:Survival Analysis
chemical_list: D004251:DNA Transposable Elements; D011392:Proline; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D011394:Proline Oxidase