Researchers at the Ecole Polytechnique Fédérale de Lausanne (EPFL) have discovered that a rhythmic, bead-like motion inside cells, known as 'mitochondrial pearling,' plays a critical role in organizing mitochondrial DNA.
The study reveals that mitochondria briefly transform into shapes resembling pearls on a string to prevent DNA from clumping. This process ensures that nucleoids—clusters of mitochondrial DNA (mtDNA)—remain evenly spaced throughout the organelle.
Scientists have long known that mtDNA must be distributed regularly to ensure proper gene expression and reliable inheritance during cell division. However, previous theories involving mitochondrial fusion or fission failed to explain how this spacing persists even when those processes are disrupted.
A century-old anomaly rediscovered
Using super-resolution imaging and electron microscopy, the team led by Professor Suliana Manuscrip and postdoctoral fellow Juan Landoni observed these pearling events occurring several times per minute. During these bursts, the mitochondria develop constrictions that match the natural spacing of the DNA clusters.
As the mitochondria transition into this pearled state, larger clusters of mtDNA break apart and redistribute into the new, bead-like sections. Once the mitochondrion returns to its tubular shape, the DNA remains separated.
"Since Margaret Reed Lewis first sketched mitochondrial pearling in 1915, it has largely been dismissed as an anomaly linked to cellular stress," said Landoni. "Over a century later, it is emerging as an elegantly conserved mechanism at the heart of mitochondrial biology."
The researchers found that the process is regulated by calcium entry into the mitochondria and internal membrane structures. When these regulators fail, nucleoids tend to clump together.
Because mitochondrial dysfunction is linked to metabolic and neurological conditions, including Alzheimer's, Parkinson's, and liver failure, this physical mechanism offers a new target for medical research. The study suggests that cells rely on these simple physical movements to maintain the stability of their genetic material.
