Human Eggs Skip Key Metabolic Reaction

The mitochondria of immature human eggs function differently than those of other cells, according to a new study. Specifically, one of the main energy-generating complexes in these mitochondria, known as complex I, is suppressed. The researchers found the same thing in immature eggs from frogs, noting that this is only known cell type in animals without a functional complex I.

The mitochondria of immature human eggs function differently than those of other cells, according to a new study by researchers at the Centre for Genomic Regulation (CRG) in Barcelona. Specifically, one of the main energy-generating complexes in these mitochondria, known as complex I, is suppressed. The researchers found the same thing in immature eggs from frogs (Xenopus), noting that this is only known cell type in animals without a functional complex I.

The study was led by Elvan Böke, PhD, a group leader at the CRG. Their work is published in an article in the journal Nature: “Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I.”

Immature eggs, or oocytes, undergo different stages of maturation in the ovaries. At an early stage, they go into cellular arrest, remaining dormant for up to 50 years. Like all other eukaryotic cells, oocytes have mitochondria that they use to generate energy.

Complex I is the first enzyme in the series of metabolic reactions—known as the electron transport chain—that generate energy in the mitochondria. This protein complex is considered fundamental, working in the cells that constitute living organisms ranging from yeast to blue whales.

Using a combination of live imaging, proteomic, and biochemistry techniques, the team studied both human and Xenopus oocytes and found that complex I is virtually absent in both. The only other type of cell known to survive with depleted complex I levels are the cells that make up the parasitic plant mistletoe. This makes oocytes the only known animal cell type without a functional complex I.

Complex I produces reactive oxygen species (ROS), which are harmful molecules that can accumulate, damage DNA, and stress cells. By altering their metabolic activity to suppress complex I, the oocytes avoid ROS. The findings explain how human egg cells remain dormant in ovaries for decades without losing their reproductive capacity.

“Humans are born with all the supply of egg cells they have in life,” explained Aida Rodríguez-Nuevo, PhD, postdoctoral researcher at the CRG and first author of the study. “As humans are also the longest-lived terrestrial mammal, egg cells have to maintain pristine conditions while avoiding decades of wear-and-tear. We show this problem is solved by skipping a fundamental metabolic reaction that is also the main source of damage for the cell.”