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.
The mechanisms through which sperm manage their energy metabolism are poorly understood.The present study provides biochemical and morphological evidence that mitochondrial citratecarrier (CIC) is present in ejaculated human sperm and is restricted to the midpiece. The inhibitionof CIC with the specific substrate analog 1,2,3-benzenetricarboxylate resulted in the reduction ofcholesterol efflux, protein tyrosine phosphorylation, phospho-AKT, phospho-p60src, hyperactivatedmotility and acrosome reaction, suggesting a role for this mitochondrial carrier in spermphysiology. Furthermore, inhibition of CIC by 1,2,3-benzenetricarboxylate resulted in a reductionof glucose-stimulated insulin secretion and autocrine insulin secretion by sperm. Remarkably,blocking CIC also reduced glucose-6-phosphate dehydrogenase activity, probably in accordancewith its regulation on insulin secretion. Capacitation and glucose metabolism were stimulated byglucose as well as citrate, the specific substrate of CIC, implying a similar action because glucose andcitrate both induced insulin secretion by sperm. In the present finding, we discovered a new siteof action for CIC in the regulation of metabolism, and it may be assumed that CIC works with otherfactors in the regulation of sperm energy metabolism to sustain capacitation process and acrosomereaction.
The mitochondrial citrate carrier (CIC) is present and regulates insulin secretion by human male gamete.
CAPPELLO, Anna Rita;Madeo M;ANDO', Sebastiano;DOLCE, Vincenza
;Aquila S.
2012-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
