Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes. (February 2015)

• Record Type: Journal Article
• Authors: Nouzova, Marcela; Rivera-Perez, Crisalejandra; Noriega, Fernando G.
• Is Part Of: Insect biochemistry and molecular biology. Volume 57(2015:Feb.)
• Page Start: 20
• Page End: 26
• Publication Date: 2015-02
• Subjects: Allatostatin -- Mosquito -- Juvenile hormone -- Membrane citrate transport; Insect biochemistry -- Periodicals; Insects -- Physiology -- Periodicals; Insects -- Molecular aspects -- Periodicals; Biochemistry -- Periodicals; Insectes -- Biochimie -- Périodiques; Insectes -- Composition -- Périodiques; Insectes -- Physiologie -- Périodiques; Insectes -- Aspect moléculaire -- Périodiques; Biochimie -- Périodiques; Biochemistry; Insect biochemistry; Insects -- Molecular aspects; Insects -- Physiology; Periodicals; 572.8157
• DOI: 10.1016/j.ibmb.2014.12.003
• Languages: English
• ISSNs: 0965-1748

Abstract

Abstract: Aedes aegypti allatostatin-C ( Aea AST-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. Aea AST-C showed no inhibitory activity in the presence of any of the intermediate precursors of JH III indicating that the Aea AST-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 Aea AST-C, and was overridden by addition of citrate or acetate. Our results provide compelling evidence that Aea AST-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. Graphical abstract: Highlights: Allatostatin-C (AST-C) is a strong and fast reversible inhibitor of JH synthesis in mosquitoes. AST-C has no effect on the activity of JH biosynthetic enzymes. The target of AST-C is located before the entry of acetyl-CoA in the pathway. AST-C blocks the CIC carrier that transports citrate from the mitochondria to the cytosol.