Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes

Insect Biochem Mol Biol. 2015 Feb;57:20-6. doi: 10.1016/j.ibmb.2014.12.003. Epub 2014 Dec 11.

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.

Keywords: Allatostatin; Juvenile hormone; Membrane citrate transport; Mosquito.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aedes / drug effects
  • Aedes / metabolism*
  • Animals
  • Biological Transport
  • Citrates / metabolism
  • Corpora Allata / drug effects
  • Corpora Allata / metabolism
  • Female
  • Hormone Antagonists / pharmacology*
  • Juvenile Hormones / metabolism
  • Membrane Transport Proteins / metabolism
  • Mitochondria / metabolism*
  • Neuropeptides / pharmacology*
  • Sesquiterpenes / antagonists & inhibitors
  • Sesquiterpenes / metabolism*

Substances

  • Citrates
  • Hormone Antagonists
  • Juvenile Hormones
  • Membrane Transport Proteins
  • Neuropeptides
  • Sesquiterpenes
  • allatostatin
  • juvenile hormone III