Scientists Reveal Hidden Machinery of Mitochondria in Stunning Detail

Scientists in Basel revealed that energy-producing proteins in mitochondria form large supercomplexes, boosting ATP production efficiency and offering new insights into cell biology, evolution, and disease.

Mitochondria, often called the powerhouses of the cell, are responsible for producing the energy needed for nearly all vital cellular processes. Researchers at the University of Basel in Switzerland have now used cryo-electron tomography to study mitochondria in unprecedented detail, revealing new insights into their inner structure.

Their findings show that the proteins responsible for generating energy, known as respiratory complexes, do not work alone. Instead, they assemble into large structures called “supercomplexes,” which play a key role in efficiently producing ATP, the cell’s primary energy source.

Mitochondria are found in the cells of nearly all living organisms, including plants, animals, and humans. They generate energy by using the oxygen we breathe and carbohydrates from food to produce ATP, which powers essential cellular functions.

Although these respiratory complexes were discovered 70 years ago, their exact organization inside mitochondria has remained elusive until now. Using state-of-the-art cryo-electron tomography, researchers led by Dr. Florent Waltz and Prof. Ben Engel at the Biozentrum of the University of Basel were able to create high-resolution images of the respiratory chain directly inside cells at a resolution never achieved before. The results of the study are published in Science.

New insights into the cell’s powerhouses

“Our data show that the respiratory proteins organize in specific membrane regions of mitochondria, stick together, and form one main type of supercomplex,” explains Florent Waltz, SNSF Ambizione Fellow and first author of the study.

“Using the electron microscope, individual supercomplexes were clearly visible – we could directly see their structures and how they work. The respiratory supercomplexes pump protons across the mitochondrial membrane. The ATP production complexes, which act similarly to a watermill, use this flow of protons to drive ATP generation.”

Mitochondrial architecture for efficient energy production

The researchers examined mitochondria in living cells of the alga Chlamydomonas reinhardtii. “We were very surprised that all the proteins were actually organized in such supercomplexes,” says Waltz. “This architecture might make ATP production more efficient, optimize electron flow, and minimize energy loss.”

In addition to the supercomplexes, the researchers were also able to examine the membrane architecture of the mitochondria more closely. “It’s somewhat reminiscent of lung tissue: the inner mitochondrial membranes have many folds that increase the surface area to fit as many respiratory complexes as possible,” says Engel.

Perspectives into evolution and health

In the future, the researchers aim to uncover why respiratory complexes are interconnected and how this synergy enhances the efficiency of cellular respiration and energy production. The study may also offer new insights for biotechnology and health.

“By examining the architecture of these complexes in other organisms, we can gain a broader understanding of their fundamental organization,” explains Waltz. “This could not only reveal evolutionary adaptations but also help us understand why disruptions in these complexes contribute to human diseases.”

Reference: “In-cell architecture of the mitochondrial respiratory chain” by Florent Waltz, Ricardo D. Righetto, Lorenz Lamm, Thalia Salinas-Giegé, Ron Kelley, Xianjun Zhang, Martin Obr, Sagar Khavnekar, Abhay Kotecha and Benjamin D. Engel, 20 March 2025, Science.
DOI: 10.1126/science.ads8738

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