The protein catalogue gives a dynamic picture of the mitochondria, beyond what was known from humans and yeast. Credit: Dr David Furness/Keele University/SPL
Scientists have mapped in unprecedented detail the proteins that make up the mitochondria in six organisms — five single-celled parasites and one plant — spanning the eukaryotic tree of life.
The findings, described in nine papers published in Cell, Cell Press Blue, Molecular Cell and Current Biology on 1 October1–9, reveal dozens of proteins that are not found in humans but are shared among parasites, including some that cause malaria or sleeping sickness. The findings might help scientists to devise new treatments for these illnesses.
The work has also stirred a long-running debate about the origin of the mitochondrion.
Cells are swapping their mitochondria. What does this mean for our health?
Best known as the powerhouse of the eukaryotic cell because it produces energy, the mitochondrion has its own tiny DNA, which is distinct from that of the cell’s nucleus. But both mitochondrial and nuclear DNA encode the proteins that make up this organelle. Most of what is known about the mitochondria comes from human and yeast studies, says Vamsi Mootha, a mitochondrial biologist at Howard Hughes Medical Institute in Boston, Massachusetts, who led the ‘mitoproteome’ catalogues project.
Now, by analysing mitochondrial proteins in several eukaryotic branches, the team has detected more proteins that might point to unstudied molecular pathways.
Trove of parasite proteins
Mootha and his colleagues analysed the proteome of several parasites, including Giardia lamblia1, which infects about 280 million people worldwide each year and causes diarrhoea10. Giardia parasites have tiny, mitochondrion-like organelles that are notoriously difficult to study because they live inside the gut of other organisms, without oxygen, says Pavel Doležal, a cell biologist at Charles University in Prague, Czech Republic.
Mootha and his colleagues identified a total of 59 mitochondrial proteins in G. lamblia — 32 that were known to scientists before and 27 new ones1. The function of 34 of these is unknown, which is surprising, Doležal says, because “it means that there is some new metabolism that we don’t know about. And it was overlooked”.
Combining the mitoproteomes from the six organisms with those known for humans and yeasts, the researchers assembled a collection of 8,619 mitochondrial proteins that charted into 3,199 families2. Around 43% of these families have not been recorded in a giant database of proteins known as Pfam. And 33 protein families are conserved in eukaryotic pathogens but absent in humans.
These proteins can be “ideal drug targets” for precise therapies that would act on parasite proteins but not human ones, Mootha says.
Obscure origins
Researchers agree that the mitochondria emerged two billion years ago when a bacterium was engulfed by an archaeal cell and began living inside it in a mutually beneficial relationship — known as endosymbiosis. This bacterium, which later became the mitochondrion, is thought to have provided its host archaea with energy.
Masked mitochondria slip into cells to treat disease in mice