How does mitochondrial DNA affect your health?

LA JOLLA (April 10, 2026)—Some of your most important partners in life are the mitochondria that power all your cells. You and these little cellular powerhouses are in a 1.5-year evolutionary relationship—but mitochondria have brought baggage. Mitochondria brought their DNA with them when they merged with larger, more complex cells long ago, and today mitochondrial DNA influences human life.

Scientists at the Salk Institute are asking what those influences are, and their latest study reveals a new biological platform for studying mitochondrial DNA in physiology, adaptation, disease processes, and treatment development. Currently, they have used the platform to generate a library of 155 cell lines with mitochondrial DNA and to reveal the relationship between mouse development and mitochondrial function. The platform, library, and research will accelerate the development of treatments for mitochondrial disorders, as well as help scientists treat mitochondrial dysfunction in other diseases and conditions such as cancer or aging.

The lesson was published in Bulletin of the National Academy of Sciences on April 10, 2026, and is funded by federal research grants and private donations.

“Mitochondrial DNA accumulates mutations at a high rate, and more than 260 inherited mtDNA disease-causing mutations have been identified in humans,” says senior and co-author Ronald Evans, PhD, professor and director of the Gene Expression Laboratory and holder of the March of Dimes Chair in Biology and Salk Development. “Until now, the lack of samples representing these variants has limited mechanistic insight and therapeutic progress. Our new platform will allow scientists to investigate mitochondrial DNA variation in health, disease and evolution, which will enable therapeutic approaches for mitochondrial disorders.”

What are mitochondrial disorders?

Mitochondrial DNA performs a very important job of creating proteins needed for energy production—but it also has a high mutation rate, and those mutations can accumulate due to dysfunctional repair processes. Because mitochondria are essential components of every cell, their dysfunction can lead to dysfunction throughout the body, with a particularly negative impact on high-energy organs such as the brain and heart. Without enough energy in your cells, symptoms such as migraines, muscle weakness, and loss of hearing or vision may begin to appear.

The chronic and widespread impact of mitochondrial dysfunction makes it very important to study. Trying to pinpoint the consequences of specific mutations in mitochondrial DNA was a slow, laborious process over many years. Researchers can create individual mouse strains with different changes in mitochondrial DNA, with just one sample sometimes lasting years. This was a problem Salk staff scientist Weiwei Fan, PhD, noticed early in his scientific career and put his mind to the PhD student.

“This new work builds on the original platform I developed during my PhD,” says Fan, first and corresponding author of the study. That platform was inefficient—it took a long time to produce a single mutation in mitochondrial DNA.

What do biological models teach us?

Salk’s new invention is a biodegradable, stem-cell-based platform that produces mice with mutations in mitochondrial DNA. Once one of these mice is established, researchers can investigate the specific symptoms of mitochondrial DNA mutation and the mechanisms by which those symptoms appear – insight that can be used to design targeted therapies down the line.

The process starts with a protein, called mitochondrial DNA polymerase, which produces randomly modified mitochondrial DNA. That modified mitochondrial DNA is then transferred into stem cells, which can be combined with mouse embryos to create mice for study.

Using this platform, Salk’s team generated a library of 155 mitochondrial DNA mutation cells, each with its own unique impact on mitochondrial function. They then used that library to confirm that the cells could be used to produce mice with single changes in mitochondrial DNA. These mice allowed them to find a strong relationship between mitochondrial function and early embryonic development, suggesting that there is a need for basic energy for normal development.

How does this new tool change the treatment of mitochondrial disease?

“Our library is a very important phenomenon and it is very diverse, it has many species that are similar to the known species that cause about 260 human diseases,” says Fan. “And with this collection of mutated cells, we can look not only at inherited changes but also those that arise based on other stressors such as environmental cues or aging.”

A new platform and library is opening up the world of mitochondrial DNA. With the ability to rapidly reproduce mitochondrial DNA mutations, advances in the treatment of mitochondrial disease and dysfunction will come quickly, too. Mouse models are already a big step forward in the field, but researchers are also eager to tap into human models in a human-relevant setting.

“Many human diseases come with or cause mitochondrial dysfunction,” says Evans. “Progress in this field has been limited, but this new platform will lead to very important research that shows therapeutic strategies to combat mitochondrial diseases, as well as diseases or conditions associated with mitochondrial dysfunction such as cancer or aging.”

Other authors and funds

Other authors include Lillian Crossley, Hunter Robbins, Mingxiao He, Yang Dai, Morgan Truitt, Annette Atkins, and Michael Downes of Salk, and Tae Gyu Oh of Salk and the University of Oklahoma.

The work was supported by the National Institutes of Health (P01HL147835, DK057978, DK120515, 1R21OD030076, CCSG P30CA23100, CCSG P30 CA014195, CCSG P3AG0 CA014195, Office of the Navy P360, Office of the Navy, P30CA23100). Naval3076, P303190, CCSG P30 CA014195), (N00014-16-1-3159), Larry L. Hillblom Foundation, Inc. (2021-D-001-NET), Wu Tsai Human Performance Alliance, Henry L. Guenther Foundation, and Waitt Foundation.

About the Salk Center for Biological Studies
The Salk Institute is an independent, non-profit research institution founded in 1960 by Jonas Salk, the inventor of the first safe and effective polio vaccine. The Center’s mission is to conduct basic, collaborative, risk-based research that addresses society’s most pressing challenges, including cancer, Alzheimer’s disease and agricultural resilience. This basic science underpins all translational efforts, generating data that enable new medicines and new approaches around the world. Learn more at www.salk.edu.