Acanthamoeba

Microscope image of Acanthamoeba. Credit: Jonathon Stefely

Blinding Amoeba Has a Backup Power Plant That Runs Without Oxygen

In A Nutshell

  • An amoeba linked to contact lens eye infections survived at least five days with no oxygen in lab tests.
  • Researchers cataloged 1,122 mitochondrial proteins, 381 of them with no obvious human or yeast match.
  • Oxygen-starved cells, including strains from human eye infections, produced hydrogen gas.
  • A drug that blocks one oxygen-free enzyme lowered the amoeba’s energy levels, but safety and benefit in patients remain untested.

A single-celled amoeba linked to contact lens eye infections and blindness keeps going even when its oxygen is cut off. According to a new study in the journal Cell, Acanthamoeba appears to pull it off by switching on a backup system that releases hydrogen gas. In lab tests, it survived at least five days with no oxygen at all.

Acanthamoeba turns up around the world and can cause painful, infectious blindness and fatal brain abscesses. It lives in places as different as air-exposed soil and deep water with almost no oxygen. Low-oxygen pockets are expected inside the body too, in abscesses and in the cornea, especially during sleep or behind contact lenses, which are a known risk factor for the eye infection. Current drugs are toxic and poorly targeted, and surgery is frequently needed.

Scientists had suspected for years that this amoeba carried unusual oxygen-free machinery, but nobody had shown it making hydrogen. A team from Massachusetts General Hospital, Harvard Medical School, the Broad Institute, and Boston University set out to settle that. Most known mitochondria, the structures that power cells, either depend on oxygen, as in humans, or run entirely without it, as in some parasites. This amoeba’s mitochondria can do both, switching modes depending on how much oxygen is around.

Acanthamoeba Mitochondria Hold 381 Proteins With No Obvious Human or Yeast Match

Before testing what the machinery could do, researchers needed a complete parts list. They tagged the outside of the amoeba’s mitochondria with a glowing marker and used magnetic beads to pull the structures out intact. Each sample was then analyzed to identify its proteins, with statistical checks to screen out contaminants from other parts of the cell.

Microscopy added a second check. Of 76 proteins tagged and tracked, 74 landed inside the mitochondria, backing up the larger list. The final catalog holds 1,122 proteins. Of those, 741 have clear counterparts in human or yeast mitochondria, while 381 have no obvious match in either. By the team’s estimate, about 8 percent of the proteins identified through lab measurements may not belong, compared with roughly 25 percent in the raw data of an earlier 2014 effort.

Acanthamoeba’s Oxygen-Free Survival Strategy
A blinding amoeba tied to contact lens infections survived at least five days without oxygen and made hydrogen gas. (Image by StudyFinds)

Nearly All Acanthamoeba Mitochondrial Proteins Increased When Oxygen Dropped

Next, researchers grew amoeba cells under 15 different conditions, varying oxygen from normal air to almost none and changing the nutrients too. They expected most of the mitochondrial machinery to power down without oxygen, with a handful of backup proteins switching on. Instead, nearly all mitochondrial proteins increased as oxygen fell.

A specific group tied to oxygen-free energy production climbed the most, including an enzyme called HydA that can generate hydrogen gas. The cells also changed shape and lost their grip on the surface without oxygen, then returned to normal within an hour of air coming back. Without oxygen, starved amoebas could not form the tough protective shells called cysts. The authors speculate that the amoeba’s two-mode mitochondria may resemble those of the last common ancestor of animals, plants, fungi, and amoebas, a point that bears on a long-running debate over whether early mitochondria relied on oxygen.

Oxygen-Starved Acanthamoeba Produced Hydrogen Gas, Including Strains From Eye Infections

Spotting the right proteins did not prove the amoeba actually makes hydrogen, so researchers measured the gas directly. Cells kept in a sealed, oxygen-free chamber stopped dividing but stayed alive, and a hydrogen sensor picked up gas from them when researchers supplied a chemical that drives the reaction. Cells raised in regular air made none.

Mitochondria pulled out of oxygen-starved cells made more hydrogen than the same weight of whole cells, consistent with the mitochondria being the source. Thirty minutes of exposure to air cut the output, which fits what is known about this type of enzyme: oxygen shuts it down fast. The same enzyme can also run in reverse and consume hydrogen, but because its genetic activity rose as oxygen fell, the authors say hydrogen production looks like its main job, though that has yet to be confirmed in living cells.

Five lines taken from human corneal infections, spanning four genetic subtypes, recovered quickly from oxygen deprivation and made hydrogen too, showing that the trait was not limited to the laboratory reference strain.

Pathway Missing From Human Cells Offers Possible Eye Infection Drug Target

Researchers also tested nitazoxanide, an antiparasitic drug that blocks one of the enzymes in the amoeba’s oxygen-free pathway. Without oxygen, the drug lowered the cells’ energy levels in lines from human eye infections. The authors add that attacking both the oxygen-using and oxygen-free pathways at once could make an effective combination.

Because human cells lack this pathway, the authors consider it an appealing target that presumably could be attacked more safely. That safety is untested, and the study did not look at hydrogen production inside an actual infected eye.

For now, this is a laboratory result. Whether the amoeba’s backup system can become the weak spot that finally yields a safer treatment for a blinding infection is the next test.


Disclaimer: This article is for informational purposes only and is not medical advice. People with eye pain, vision changes, or concerns about an eye infection should consult a doctor or eye care professional.


Paper Notes

Limitations

Culturing and harvesting large quantities of cells, which this approach requires, works for a lab-friendly organism like Acanthamoeba but would not suit organisms that cannot be grown at scale. The study focused on the active, free-moving form, called a trophozoite, because current methods cannot isolate mitochondria from the cyst form, whose cell wall is extremely durable. Hydrogen production was shown in laboratory cultures under experimental oxygen-free conditions. The authors note that the main direction in which the hydrogen enzyme works in living amoebas under varying conditions, and the molecules that supply its electrons, remain to be determined. They also acknowledge that limits in current methods for tracing evolutionary history may affect conclusions spanning very long timescales. The nitazoxanide experiment measured cellular energy levels in lab cultures and did not test safety or effectiveness in patients.

Funding and Disclosures

Support came from the Howard Hughes Medical Institute Emerging Pathogens Initiative, Mark and Lisa Schwartz, and the National Institutes of Health, with additional financial support from Dean Cataldo Leone of Boston University. Electron microscopy was performed at the Harvard Medical School Electron Microscopy Facility. The paper states that its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author Vamsi K. Mootha discloses serving as a paid advisor to 5am Ventures and Falcon Bio and sitting on the advisory board of Cell. The authors state they used ProofigAI software to check image integrity.

Publication Details

This study, titled “Mitochondrial proteome of Acanthamoeba delineates aerobic and anaerobic pathways dynamically regulated by oxygen,” was published in Cell, Volume 189, pages 6246 through 6266, on October 1, 2026, after acceptance on August 28, 2026. Authors include Jonathan A. Stefely, Felicia G. Deng, Michael Z. Chen, and colleagues, including members of the MitoCarta Tree of Life Consortium, with corresponding authors Namrata D. Udeshi, John Samuelson, and Vamsi K. Mootha. The DOI is https://doi.org/10.1016/j.cell.2026.08.056. The article is open access under a CC BY license.

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