Scientists at EPFL report that a transient shape change in mitochondria—known as “pearling,” in which the organelle briefly forms bead-like constrictions—can redistribute clusters of mitochondrial DNA (mtDNA) into more evenly spaced nucleoids. The work, published April 2, 2026 in Science, suggests the process is triggered by calcium influx into mitochondria and may help explain how cells maintain robust mtDNA organization, a feature implicated in a range of mitochondrial-related disorders.
Mitochondria, often described as the cell’s power plants, carry their own genetic material—mitochondrial DNA (mtDNA). Cells typically contain hundreds to thousands of copies of mtDNA, packaged into clusters called nucleoids.
Scientists have long observed that nucleoids are regularly spaced within mitochondria, a pattern thought to support reliable inheritance of mtDNA during cell division and more uniform gene expression along the organelle.
In a study led by Suliana Manley of EPFL’s Laboratory of Experimental Biophysics, researchers argue that commonly proposed explanations—such as mitochondrial fusion, fission or molecular tethering—do not fully account for the persistence of this spacing, including under conditions when those mechanisms are disrupted.
To investigate how spacing is maintained, the team combined super-resolution imaging with correlated light and electron microscopy and phase-contrast microscopy to follow mitochondrial shape changes and individual nucleoids in living cells.
The researchers report that mitochondria can undergo “pearling” events a few times per minute, temporarily forming a series of evenly spaced constrictions that resemble beads on a string. The spacing between these constrictions closely matches typical nucleoid-to-nucleoid distances. During pearling, larger nucleoid clusters were observed splitting into smaller units that occupy neighboring “pearls,” and after mitochondria returned to a tubular shape, the redistributed nucleoids could remain separated.
Using genetic and pharmacological approaches, the study links pearling to calcium entering mitochondria and reports that internal membrane organization helps maintain nucleoid separation. When these regulatory elements were disrupted, the researchers observed nucleoids tending to clump into aggregates rather than remaining evenly distributed.
Juan Landoni, a postdoctoral researcher involved in the work, said the phenomenon dates back more than a century, noting that cell biologist Margaret Reed Lewis sketched mitochondrial pearling in 1915. According to the team, pearling was long treated as an oddity associated with cellular stress, but their findings support a broader role for the process in organizing mtDNA.
The authors argue that the results highlight how physical shape changes can work alongside molecular machinery to organize cellular components. EPFL’s research summary notes that mitochondrial and mtDNA dysfunction are associated with metabolic and neurological disorders—including conditions such as liver failure and encephalopathy—and are also linked in the scientific literature to aging-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s, though the study itself focuses on mechanisms of mtDNA organization rather than demonstrating a direct causal role for pearling in those diseases.
