Too Much RNA Can Damage Mitochondria and Drain Cell Energy

The work was published in 2026 in the Proceedings of the National Academy of Sciences. It is basic cell biology, done in cells and in mitochondria purified from cells. It is not a study in people or animals.

Mitochondria are the structures inside cells that make most of a cell's usable energy. The team, led by Brahim Belhaouari and Zhilong Yang at Texas A&M, studied vaccinia virus. This poxvirus is the prototype poxvirus and the basis of the smallpox and mpox vaccines. It carries two enzymes, called decapping enzymes, that help break down RNA in infected cells. It works alongside a host cell enzyme that also degrades RNA.

Earlier research mostly treated this RNA breakdown as a way for the virus to control its own genes and avoid immune detection. This study asked a different question: what happens to mitochondria when the breakdown fails?

When the viral enzymes or the cellular enzyme were depleted, mitochondrial respiration and integrity were severely compromised. Respiration is the process mitochondria use to make energy.

The authors then showed that building up extra double-stranded RNA and messenger RNA is enough, on its own, to cause profound defects in mitochondrial respiration and integrity. This included RNA carrying pseudouridine modifications, a chemical change to the RNA.

The damage did not depend on the usual immune alarm. The study says it occurred independently of interferon induction and of Protein Kinase R, a sensor of double-stranded RNA. Excess RNA also suppressed respiration in purified mitochondria removed from cells, and it physically associated with mitochondria. Together, the authors say, this supports a mechanism that does not involve the immune system.

The proposed explanation is a loss of electrical balance. Mitochondria keep a charge difference, called a membrane potential, across their membranes. This drives energy production. The study found that excess messenger RNA and doublestranded RNA reduced this potential in both cells and purified mitochondria. The authors say this points to disruption of the proton gradient as the cause of the impaired respiration.

In comments reported by ScienceDaily, Yang said the team thinks negatively charged RNA may gather around mitochondria and upset their electrical balance. He added that how this happens is unknown and is a new concept the group is still exploring.

For longevity-minded readers, the interest is the possible link between RNA handling and cellular energy. The ScienceDaily coverage notes that abnormal RNA buildup has been seen in some cancers, neurodegenerative diseases and agingrelated disorders. That connection goes beyond what the study tested. The experiments were in vaccinia virus infection, and the coverage itself says more work is needed to learn how widely this occurs and whether it contributes to any of those diseases.

The study also does not show that mRNA vaccines harm mitochondria in people. The experiments did not test vaccines. They looked at cells where RNA breakdown was impaired, and at RNA added to isolated mitochondria. The authors say the findings have implications for RNA-based therapeutics and vaccines, which is a reason for further research, not a finding of harm.

What to watch next

Studies that identify how RNA disrupts the mitochondrial membrane potential, and whether the same effect appears in uninfected cells, animals and human tissue.

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