How mitochondria organize their DNA to sustain cellular energy

Researchers from the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, led by Suliana Manley, and colleagues including Juan C. Landoni, Matthew D. Lycas, Josefa Macuada, Willi Stepp, Roméo Jaccard, Christopher J. Obara, Andrew S. Moore, David Hoffman, Jennifer Lippincott-Schwartz, Wallace Marshall, and Gabriel Sturm.

The work was published in the journal Science on April 2, 2026.

What did researchers observe?

Mitochondria contain small circular DNA molecules grouped into compact structures called nucleoids. These nucleoids are regularly spaced along the mitochondrial network rather than randomly distributed.

Mitochondria contain small DNA clusters called nucleoids. The team found that these nucleoids are evenly spaced along mitochondria, rather than randomly distributed. This spatial organization is actively maintained and is essential for mitochondrial efficiency.

Using advanced live-cell imaging, the scientists showed that mitochondria undergo a physical process called “pearling” , transient bead-like constrictions that help distribute nucleoids regularly along the mitochondrial network.

This ordered distribution ensures:

• Balanced mitochondrial gene expression
• Efficient energy production
• Proper inheritance of mitochondrial DNA during cell division

When this organization is disrupted, mitochondrial function becomes uneven, potentially leading to cellular dysfunction.

A physical mechanism, not just genetics

The study demonstrates that biophysical forces inside mitochondria help control DNA positioning. This means mitochondrial performance depends not only on genetic content, but also on how that DNA is physically organized.

The implications

This mechanism may help explain mitochondrial dysfunction observed in:

• Aging
• Neurodegenerative diseases
• Metabolic disorders

It also opens the possibility of targeting mitochondrial structure - not only mitochondrial genes - as a future therapeutic strategy.

Mitochondria maintain cellular energy by carefully spacing their DNA. This spatial organization is an active, physical process that directly supports mitochondrial function and cellular health.

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Reference

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