title: Aldehyde dehydrogenase 3 converts farnesal into farnesoic acid in the corpora allata of mosquitoes.
abstract: The juvenile hormones (JHs) play a central role in insect reproduction, development and behavior. Interrupting JH biosynthesis has long been considered a promising strategy for the development of target-specific insecticides. Using a combination of RNAi, in vivo and in vitro studies we characterized the last unknown biosynthetic enzyme of the JH pathway, a fatty aldehyde dehydrogenase (AaALDH3) that oxidizes farnesal into farnesoic acid (FA) in the corpora allata (CA) of mosquitoes. The AaALDH3 is structurally and functionally a NAD(+)-dependent class 3 ALDH showing tissue- and developmental-stage-specific splice variants. Members of the ALDH3 family play critical roles in the development of cancer and Sjögren-Larsson syndrome in humans, but have not been studies in groups other than mammals. Using a newly developed assay utilizing fluorescent tags, we demonstrated that AaALDH3 activity, as well as the concentrations of farnesol, farnesal and FA were different in CA of sugar and blood-fed females. In CA of blood-fed females the low catalytic activity of AaALDH3 limited the flux of precursors and caused a remarkable increase in the pool of farnesal with a decrease in FA and JH synthesis. The accumulation of the potentially toxic farnesal stimulated the activity of a reductase that converted farnesal back into farnesol, resulting in farnesol leaking out of the CA. Our studies indicated AaALDH3 plays a key role in the regulation of JH synthesis in blood-fed females and mosquitoes seem to have developed a "trade-off" system to balance the key role of farnesal as a JH precursor with its potential toxicity.
authors: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors: Crisalejandra
authors: C
authors: Rivera-Perez
authors: Marcela
authors: M
authors: Nouzova
authors: Mark E
authors: ME
authors: Clifton
authors: Elena Martin
authors: EM
authors: Garcia
authors: Elizabeth
authors: E
authors: LeBlanc
authors: Fernando G
authors: FG
authors: Noriega
mesh_terms: D000330:Aedes / Q000201:enzymology*; D000367:Age Factors; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D003335:Corpora Allata / Q000201:enzymology*; D005204:Farnesol / Q000031:analogs & derivatives* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D007605:Juvenile Hormones / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D007605:Juvenile Hormones; D012333:RNA, Messenger; D005204:Farnesol; C007702:farnesoic acid; D000445:Aldehyde Oxidoreductases; C040715:farnesal dehydrogenase; D000444:Aldehyde Dehydrogenase; C084519:farnesal
keywords: Aedes aegypti; Aldehyde dehydrogenase 3; Aldo-keto reductase; Corpora allata; Farnesal; Juvenile hormone; Mosquito; RNAi
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