What sperm can teach us about energy production

Abstract

Mammalian sperm have evolved under strict selection pressures that have resulted in a highly polarized and efficient design. A critical component of that design is the compartmentalization of specific metabolic pathways to specific regions of the cell. Although the restricted localization of mitochondria to the midpiece is the best known example of this design, the organization of the enzymes of glycolysis along the fibrous sheath is the primary focus of this review. Evolution of variants of these metabolic enzymes has allowed them to function when tethered, enabling localized energy production that is essential for sperm motility. We close by exploring how this design might be mimicked to provide an energy-producing platform technology for applications in nanobiotechnology.

Fig. 1

A representative mammalian sperm (domestic dog, Canis lupus familiaris) showing the highly polarized structure associated with this cell type. The head and flagellum are the two major regions of the cell, and the flagellum is itself composed of three distinct and easily identifiable regions: the midpiece, principal piece, and endpiece

Fig. 2

Glycolysis in murine spermatozoa. The reactions of glycolysis are diagrammed using the forms of the glycolytic enzymes that are believed to be present in the principal piece of murine sperm. Note that although not truly a part of glycolysis itself, lactate dehydrogenase is included in the diagram because its function is essential for regeneration of NAD⁺

Fig. 3

Oriented immobilization of GPI resulted in improved binding and higher specific activity. (a) Placement of a binding peptide (a repeat of six histidine residues, 6× His tag) enabled oriented immobilization as the tag bound nickel tethered to the gold surface via nitrilotriacetic acid (Ni-NTA). (b) When the His tag was removed, GPI adsorbed to the surface in random orientations. (c) Approximately twice as much GPI bound to the chip surfaces when the His tag was present. (d) Of interest, the specific activity of GPI bound using oriented immobilization was approximately ninefold higher than that adsorbed to the surface randomly. A single asterisk denotes statistical significance at p = 0.012, whereas the double asterisk denotes statistical significance at p = 0.006. Figure modified from Mukai et al. 2009

Fig. 4

Coupled reaction of tethered His-HK and His-GPI. (a) Both HK and GPI were immobilized on a gold surface in oriented fashion using a 6× His tag binding to Ni-NTA. (b) Using coupled biochemical reactions, the activity in series of HK and GPI was observed as a change in absorbance at 340 nm. Control chips with either HK alone or GPI alone did not show this activity and yielded results identical to a buffer alone control