Scientists at the Broad Institute and partner institutions have built the largest map yet of mitochondrial proteins across different forms of life. Their work goes far beyond the old idea of mitochondria as simple energy makers. The new catalog points to hidden roles for these organelles and flags dozens of proteins in disease-causing parasites that could be targeted by new drugs.
This project stands out for its reach and detail. The MitoCarta Tree of Life team, with researchers from the Broad Institute, Mass General Brigham, Harvard Medical School, Harvard T.H. Chan School of Public Health, and Boston University Henry M. Goldman School of Dental Medicine, mapped the mitochondrial proteomes of one plant and five single-celled pathogens. Their results, published in nine papers in Cell and related journals, challenge the old textbook view of mitochondria.
The first major MitoCarta reference was created in 2008 and included about 1,100 mammalian mitochondrial proteins, laying the groundwork for later disease gene discovery and comparative studies.
Comparative proteomics reveals surprises
The team used next-generation mass spectrometry to break down the mitochondrial protein lists of Arabidopsis and five parasites. The new inventory is much bigger than any before. It also finds proteins unique to pathogens and missing in humans. These are prime targets for new anti-infective drugs. Project leader Vamsi Mootha said the group “repurposed everything we’ve learned over the last 15 years characterizing the mammalian mitoproteome” to build a new base for comparing mitochondria across life.
One example stands out. Giardia, a parasite that causes diarrhea, has mitochondria stripped down to just 59 proteins. It lacks the usual energy-making machinery. This “remnant” organelle breaks the classic definition of mitochondria. It hints at a much more flexible evolutionary story. In contrast, Acanthamoeba—an organism that can cause blindness—has the most complex energy system seen so far. It can switch between using oxygen and surviving without it, depending on what’s available.
Evolution and drug discovery
The team didn’t stop at cataloging. They retrained machine learning tools to predict mitochondrial proteomes for hundreds of other species. The timeline they built supports the idea that mitochondria appeared relatively late in eukaryotic evolution. This adds a new twist to the debate about how complex life began. It’s a shift on par with the single-cell brain atlas that changed Alzheimer’s research.
For drug developers, the findings are immediate. Pathogen-specific mitochondrial proteins—especially in parasites like Leishmania and Trypanosoma, whose mitochondrial proteomes are 50 percent larger than those in humans—offer new ways to attack neglected tropical diseases. The team’s new methods for studying Babesia, a tick-borne parasite, could also speed up research on malaria and toxoplasmosis.
For Acanthamoeba, researchers reported an AcMitoCarta catalog of 1,122 mitochondrial proteins, including 381 proteins with no clear homologs in human or yeast mitochondria.
Open data, open questions
Even with this huge leap, more than half the proteins in the catalog have unknown functions. The consortium has made all data free to access at mitocarta.org. Researchers worldwide can dig into this resource for new biology and drug leads. Sarah Calvo, senior computational scientist at the Broad, called the project a step toward answering “one of the deepest questions: How did complex life evolve on our planet?”
The MitoCarta Tree of Life gives scientists a new way to compare mitochondria across species. The diversity found here shows that even familiar cell parts can still surprise. The next big drug breakthrough might start in these overlooked corners of the cell.
A Technology Networks report notes that the nine scientific papers include both research and commentary, with the main study published in Cell (DOI 10.1016/j.cell.2026.08.029). The Broad Institute and professional journals point out that some mitochondrial proteins found in pathogens are missing in humans and are now being considered as possible targets for new anti-infective drugs, including those for tropical diseases.
