title: The mitochondrial citrate carrier (CIC) is present and regulates insulin secretion by human male gamete.
abstract: The mechanisms through which sperm manage their energy metabolism are poorly understood. The present study provides biochemical and morphological evidence that mitochondrial citrate carrier (CIC) is present in ejaculated human sperm and is restricted to the midpiece. The inhibition of CIC with the specific substrate analog 1,2,3-benzenetricarboxylate resulted in the reduction of cholesterol efflux, protein tyrosine phosphorylation, phospho-AKT, phospho-p60src, hyperactivated motility and acrosome reaction, suggesting a role for this mitochondrial carrier in sperm physiology. Furthermore, inhibition of CIC by 1,2,3-benzenetricarboxylate resulted in a reduction of glucose-stimulated insulin secretion and autocrine insulin secretion by sperm. Remarkably, blocking CIC also reduced glucose-6-phosphate dehydrogenase activity, probably in accordance with its regulation on insulin secretion. Capacitation and glucose metabolism were stimulated by glucose as well as citrate, the specific substrate of CIC, implying a similar action because glucose and citrate both induced insulin secretion by sperm. In the present finding, we discovered a new site of action for CIC in the regulation of metabolism, and it may be assumed that CIC works with other factors in the regulation of sperm energy metabolism to sustain capacitation process and acrosome reaction.
authors.affiliation: Department of Pharmaco-Biology, Faculty of Pharmacy, University of Calabria, Arcavacata di Rende-CS 87036, Italy.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Cappello
authors.forename: Carmela
authors.initials: C
authors.lastname: Guido
authors.forename: Antonella
authors.initials: A
authors.lastname: Santoro
authors.forename: Marta
authors.initials: M
authors.lastname: Santoro
authors.forename: Loredana
authors.initials: L
authors.lastname: Capobianco
authors.forename: Daniela
authors.initials: D
authors.lastname: Montanaro
authors.forename: Marianna
authors.initials: M
authors.lastname: Madeo
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolce
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
mesh_terms: D020101:Acrosome Reaction / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013075:Sperm Capacitation / Q000502:physiology; D013081:Sperm Motility / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D007328:Insulin; C020723:citrate-binding transport protein; D002784:Cholesterol; D011505:Protein-Tyrosine Kinases