Special subunit meets energy demands for spermatogenesis

Published September 01 2016

Images of mouse seminiferous tubule showing nuclei (blue), the synaptonemal complex from spermatocytes (green), and the MPC1-like subunit in mitochondria (orange/red). PHOTO COURTESTY OF BENOÎT VANDERPERRE

The balance between glycolysis and oxidative phosphorylation plays a central role in many cellular processes, such as cell function, cell fate and disease progression. Pyruvate, a product of glycolysis that acts as an electron donor for oxidative phosphorylation, links these two pathways together. In a recent paper published in the Journal of Biological Chemistry, Benoît Vanderperre and colleagues at the University of Geneva in Switzerland discovered a new subunit for the complex that carries pyruvate across the inner mitochondrial membrane. The subunit appears to be found only in placental mammals and is thought to play a role in meeting the energy demands of spermatogenesis.

Glycolysis and oxidative phosphorylation are vital for cellular energy production. Glycolysis breaks down sugar to form precursors for other metabolic pathways, a small amount of ATP and pyruvate. Oxidative phosphorylation is responsible for the majority of ATP production within the mitochondria and uses pyruvate as an electron donor. Understanding how pyruvate is transported within the cell is important for appreciating how cytosolic and mitochondrial metabolism are coordinated and how metabolic processes are important for cell fate and function.

Pyruvate is transported across the inner mitochondrial membrane by a complex called the mitochondrial pyruvate carrier. MPC is made up of two subunits, MPC1 and MPC2. Studies with yeast have uncovered a third MPC subunit involved in the switch between fermentation and respiration, but characterization of the MPC in higher eukaryotes remains incomplete. This led to the search for other components that may make up the MPC in higher eukaryotes.

Vanderperre and colleagues discovered the new subunit, called MPC1-like, or MPC1L for short, while searching for proteins similar to the MPC1 and MPC2 nucleotide sequences. The investigators found there is a high degree of sequence conservation between MPC1 and MPC1L, with slight variations in the length of the C-terminus.

Genes with high-sequence similarity do not always behave analogously at the protein level, so the team set out to determine the correspondence between MPC1 and MPC1L. They began by looking at subcellular localization of MPC1L using immunofluorescence. The immunofluorescence data showed that MPC1L is a membrane protein inserted in the inner mitochondrial membrane with a topology and structure that parallels that of MPC1. Using bioluminescence resonance energy transfer and respirometry experiments that monitored pyruvate flux, the investigators also were able to show that MPC1L not only can interact physically with MPC2, the other subunit in the MPC complex, but also forms a functional complex. This functional complex is able to facilitate pyruvate import into the mitochondria at rates comparable to the MPC1/MPC2 complex.

So if MPC1 and MPC1L have similar functions at similar efficacies, why does the cell expend energy to make both of them? It turns out that, while their functions are similar, their expression patterns are not. MPC1 is expressed ubiquitously, while MPC1L is highly expressed in the testes and may also be expressed in fetal heart and ovaries.

This raises questions about the role of MPC1L in spermatogenesis and how it may be linked to cell fate determination and function in this specific cell type. Metabolic processes have been shown to play important roles in differentiation, so Vanderperre and colleagues speculate that the extra expression of MPC1L could help meet higher demands for MPC function during spermatogenesis in placental mammals.

Amber Lucas Amber Lucas is a graduate student at Carnegie Mellon University.