Mitochondrial Protein Map Reveals New Parasite Drug Targets and Clues to Mitochondria’s Origins

Scientists have mapped the mitochondrial proteins of six organisms across the eukaryotic tree of life: five unicellular parasites and one plant. The survey revealed dozens of proteins that are absent from humans but shared among parasites, including organisms that cause malaria and sleeping sickness.

The findings could help researchers develop treatments that target parasite proteins without affecting human cells. The study also adds evidence to a long-standing debate about how mitochondria originated.

Why mitochondria matter

Mitochondria are best known as the energy-producing “powerhouses” of eukaryotic cells. They also contain a small amount of DNA that is distinct from the DNA in the cell nucleus. Both mitochondrial and nuclear DNA encode proteins that make up the organelle.

Most knowledge about mitochondria comes from studies of humans and yeast, says Vamsi Moosa, a mitochondrial biologist at the Howard Hughes Medical Institute in Boston, Massachusetts, who led the Mitoproteome catalog project.

By analyzing mitochondrial proteins across several branches of the eukaryotic tree of life, Moosa and his colleagues identified additional proteins that could be involved in previously unstudied molecular pathways.

A trove of previously unknown parasite proteins

One of the organisms analyzed was Giardia lamblia, a parasite that infects approximately 280 million people worldwide each year and causes diarrhea.¹¹⁰

Parasites can be difficult to study because they have tiny mitochondria and often live in oxygen-poor environments, including the guts of other organisms.

For G. lamblia, the researchers identified 59 mitochondrial proteins: 32 that were already known and 27 that had not previously been identified.¹ The functions of 34 proteins remain unknown, suggesting that the parasite may rely on metabolic processes that scientists have not yet characterized.

By combining the mitochondrial protein catalogs of the six newly analyzed organisms with existing data from humans and yeast, the researchers assembled a collection of 8,619 mitochondrial proteins organized into 3,199 families.²

Approximately 43% of these protein families are not recorded in Pfam, a large database of protein families. In addition, 33 protein families are conserved in eukaryotic pathogens but absent from humans.

These pathogen-specific proteins could become precise drug targets, allowing treatments to attack parasites while avoiding human proteins.

What the protein catalog says about mitochondrial origins

Researchers generally agree that mitochondria emerged around two billion years ago, when bacteria were engulfed by archaeal cells and began living inside them in a mutually beneficial relationship known as endosymbiosis.

The bacterium that eventually became the mitochondrion is thought to have supplied energy to its archaeal host. Comparing mitochondrial proteins across diverse eukaryotes could help scientists determine which features were present early in the organelle’s history and which evolved later.