Speract, a sea urchin egg peptide that regulates sperm motility, also stimulates sperm mitochondrial metabolism.

Sea urchin sperm have only one mitochondrion, that in addition to being the main source of energy, may modulate intracellular Ca(2+) concentration ([Ca(2+)]i) to regulate their motility and possibly the acrosome reaction. Speract is a decapeptide from the outer jelly layer of the Strongylocentrotus purpuratus egg that upon binding to its receptor in the sperm, stimulates sperm motility, respiration and ion fluxes, among other physiological events. Altering the sea urchin sperm mitochondrial function with specific inhibitors of this organelle, increases [Ca(2+)]i in an external Ca(2+) concentration ([Ca(2+)]ext)-dependent manner (Ardón, et al., 2009. BBActa 1787: 15), suggesting that the mitochondrion is involved in sperm [Ca(2+)]i homeostasis. To further understand the interrelationship between the mitochondrion and the speract responses, we measured mitochondrial membrane potential (ΔΨ) and NADH levels. We found that the stimulation of sperm with speract depolarizes the mitochondrion and increases the levels of NADH. Surprisingly, these responses are independent of external Ca(2+) and are due to the increase in intracellular pH (pHi) induced by speract. Our findings indicate that speract, by regulating pHi, in addition to [Ca(2+)]i, may finely modulate mitochondrial metabolism to control motility and ensure that sperm reach the egg and fertilize it.

Soluble adenylyl cyclase of sea urchin spermatozoa.

Fertilization, a key step in sexual reproduction, requires orchestrated changes in cAMP concentrations. It is notable that spermatozoa (sperm) are among the cell types with extremely high adenylyl cyclase (AC) activity. As production and consumption of this second messenger need to be locally regulated, the discovery of soluble AC (sAC) has broadened our understanding of how such cells deal with these requirements. In addition, because sAC is directly regulated by HCO(3)(-) it is able to translate CO2/HCO(3)(-)/pH changes into cAMP levels. Fundamental sperm functions such as maturation, motility regulation and the acrosome reaction are influenced by cAMP; this is especially true for sperm of the sea urchin (SU), an organism that has been a model in the study of fertilization for more than 130 years. Here we summarize the discovery and properties of SU sperm sAC, and discuss its involvement in sperm physiology. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.

Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochrome c oxidase.

Experimentally relocating mitochondrial genes to the nucleus for functional expression (allotopic expression) is a challenging process. The high hydrophobicity of mitochondria-encoded proteins seems to be one of the main factors preventing this allotopic expression. We focused on subunit II of cytochrome c oxidase (Cox2) to study which modifications may enable or improve its allotopic expression in yeast. Cox2 can be imported from the cytosol into mitochondria in the presence of the W56R substitution, which decreases the protein hydrophobicity and allows partial respiratory rescue of a cox2-null strain. We show that the inclusion of a positive charge is more favorable than substitutions that only decrease the hydrophobicity. We also searched for other determinants enabling allotopic expression in yeast by examining the COX2 gene in organisms where it was transferred to the nucleus during evolution. We found that naturally occurring variations at within-membrane residues in the legume Glycine max Cox2 could enable yeast COX2 allotopic expression. We also evidence that directing high doses of allotopically synthesized Cox2 to mitochondria seems to be counterproductive because the subunit aggregates at the mitochondrial surface. Our findings are relevant to the design of allotopic expression strategies and contribute to the understanding of gene retention in organellar genomes.

[Congenital heart disease, heterotaxia and laterality]. / Malformaciones cardíacas, heterotaxia y lateralidad.

Congenital heart disease occurs in about 0,8% of all newborns. Many cardiac malformations occur among relatives and have a polymorphic presentation. The origin of most congenital heart disease is thought to be multifactorial, implying both anomalous expression of genes and the influence of epigenetic factors. However, in a small number of cases, the origin of congenital heart disease has been directly related to chromosomal anomalies or to defects in a single gene. Curiously, defects in a single gene can explain a polymorphic presentation if the anomalous gene controls a basic embryonic process that affects different organs in time and space. Some of these genes appear to control the establishment of laterality. The establishment of the left-right asymmetry starts at the Hensen node. Here, the initial embryonic symmetry is broken by cascades of gene activation that confer specific properties on the left and right sides of the embryo. Although there are variations between species, some basic patterns of gene expression (Nodal, Pitx2) appear to be maintained along the phylogenetic scale. Anomalous expression of these genes induces the heterotaxia syndrome, which usually courses with congenital heart disease. The development of heart malformations is illustrated with the mouse mutant iv/iv, which is a model for the heterotaxia syndrome and the associated congenital heart disease.