Mitochondrial Replication Mechanism Identified

In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood.

Investigators at the University of California, Davis (USA) labeled mitochondria, their chromosomes, and the endoplasmic reticulum with fluorescent dyes and employed microscopy to follow their movements during mitosis.

Results published in the July 15, 2016, online edition of the journal Science revealed that dividing mitochondrial chromosomes were located at points where the endoplasmic reticulum touched the outside of a mitochondrion. These sites also became the points where mitochondria divided into two offspring.

At ER-mitochondria contact points, the consecutive events of mtDNA replication, mitochondrial division, and mitochondrial motility were connected together to ensure the accurate distribution of nucleoids within cells. The findings suggested that these ER-mitochondria contact points coordinated the licensing of mtDNA replication with downstream mitochondrial division events to distribute newly replicated mtDNA to daughter mitochondria.

"This has very profound implications for human disease," said senior author Dr. Jodi Nunnari, professor of molecular and cellular biology at the University of California, Davis. "The endoplasmic reticulum comes into contact with the mitochondrion, and where they contact is where they divide. There are hundreds of contact points around the cell that determine where division takes place and how mitochondria are distributed, but division preferentially occurs at the subset of contacts where mitochondrial DNA is being copied. It shows that there is a higher order to this, it is not simply random."

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University of California, Davis