title: Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes.
abstract: Aedes aegypti allatostatin-C (AeaAST-C or PISCF-AST) is a strong and fast reversible inhibitor of juvenile hormone III (JH III) synthesis by the corpora allata (CA) of mosquitoes; however, its mechanism of action remains poorly understood. AeaAST-C showed no inhibitory activity in the presence of any of the intermediate precursors of JH III indicating that the AeaAST-C target is located before the entry of acetyl-CoA in the pathway. Stimulation experiments using different sources of carbon (glucose, pyruvate, acetate and citrate) suggest that AST-C acts after pyruvate is transformed to citrate in the mitochondria. In vitro inhibition of the citrate mitochondrial carrier (CIC) mimicked the effect of AeaAST-C, and was overridden by addition of citrate or acetate. Our results provide compelling evidence that AeaAST-C inhibits JH III synthesis by blocking the CIC carrier that transports citrate from the mitochondria to the cytosol, obstructing the production of cytoplasmic acetyl-CoA that sustains JH III synthesis in the CA of mosquitoes.
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: Marcela
authors.initials: M
authors.lastname: Nouzova
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: Crisalejandra
authors.initials: C
authors.lastname: Rivera-Perez
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA. Electronic address: noriegaf@fiu.edu.
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Noriega
mesh_terms: D000330:Aedes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002951:Citrates / Q000378:metabolism; D003335:Corpora Allata / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D007605:Juvenile Hormones / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002951:Citrates; D006727:Hormone Antagonists; D007605:Juvenile Hormones; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012717:Sesquiterpenes; C076523:allatostatin; C036585:juvenile hormone III
keywords: Allatostatin; Juvenile hormone; Membrane citrate transport; Mosquito