JUL 18, 2016 08:57 AM PDT

Scientists Learn How Mitochondrial DNA Replication is Controlled

WRITTEN BY: Carmen Leitch
Many human diseases have been linked to dysfunction in mitochondria, organelles in every cell that are responsible for generating energy, and which have their own set of DNA that they maintain themselves. It’s been unknown however, how the replication of that mitochondrial DNA (mtDNA) is controlled in mammalian cells. Publishing in Science, researchers have now made an important discovery in determining how cells control the replication of mtDNA and couple that process to mitochondrial division.
ER-mitochondria contacts coordinate mtDNA replication with mitochondrial division. In human cells, a subset of ER-mitochondria contacts are spatially linked to mitochondrial nucleoids engaged in replication and are destined for mitochondrial division./ Credit: Science, Lewis et al
It’s thought that mitochondria originated from a bacterium that took up residence inside of other cells, permanently, and have retained their own DNA from that very distant past. All eukaryotic cells use mitochondria to obtain energy from the metabolic process known as respiration.

"This has very profound implications for human disease," said Jodi Nunnari, Professor and Chair of Molecular and Cellular Biology at the University of California, Davis and the senior author of the paper. Division of DNA contained in the cell's nucleus is very tightly controlled, but synthesis and division of mtDNA is "a lot more relaxed," explained Nunnari.

The cell must somehow organize new copies of mtDNA. Mitochondria have the appearance of long, snaking tubes in human cells. From hundreds to thousands of copies of their single chromosome are packaged into a structure called the nucleoid.

Two of the investigators, postdoctoral researcher Samantha Lewis, together with undergraduate student Lauren Uchiyama, tagged mitochondria, their chromosomes, and the endoplasmic reticulum, a network of tubes that spreads throughout the cell, with fluorescent dyes so they could be observed under a microscope.
Replicating nucleoids mark sites of ER-mediated division. Representative time-lapse images of a U2OS cell expressing mito-BFP, mRuby-KDEL (ER), and POLG2-GFP, demonstrating mitochondrial division at a mitochondrial-ER contact site spatially linked to POLG2-labeled nucleoid (arrowheads indicate division site). / Credit: Science, Lewis et al
They observed that when mitochondrial chromosomes were dividing, they were located at points where the endoplasmic reticulum touches a mitochondrion. Those were the same points where mitochondria divided into two, a process whereby a protein encircles the organelle, then squeezes it until it splits.

"The endoplasmic reticulum comes into contact with the mitochondrion, and where they contact is where they divide," Nunnari said.

This contact between the organelles "licenses" the mtDNA to replicate and divide, Nunnari explained. The DNA division is physically coupled to division of the mitochondrion itself, as well as to the distribution of the new, daughter DNA around the cell.

"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" Nunnari continued. "It shows that there is a higher order to this, it is not simply random."

Nunnari commented that this work stemmed entirely from fundamental research, but the discovery has many implications for understanding cellular functions, aging and a broad range of diseases.
"We didn't come to this by studying any specific disease, it's discovery-based research, but this will greatly impact human health," Nunnari concluded.

Sources: Science, Science Daily via University of California, Davis
About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 12, 2018
Microbiology
NOV 12, 2018
Some Bacteria Gain Resistance Even Without Exposure to Antibiotics
Most bacteria are harmless, some are even beneficial to us. But some of the dangerous ones pose a real threat to public health....
NOV 19, 2018
Neuroscience
NOV 19, 2018
Researchers identify neural pathways that control behavioral responses to noxious stimuli
Behavioral responses to the pain perception could range from reflexive withdrawal to more complex behaviors to avoid or decrease the pain. Neurons in the lateral division of the parabrachial...
NOV 21, 2018
Immunology
NOV 21, 2018
HIV Persisting How?
A team of researchers have identified an HIV reservoir...
NOV 24, 2018
Genetics & Genomics
NOV 24, 2018
Alzheimer's Researchers Detect Genetic Recombination in the Brain
Our genomic sequence is thought to remain the same throughout our lives. But new research has found evidence to the contrary....
DEC 10, 2018
Neuroscience
DEC 10, 2018
Vitamin D and Schizophrenia
with vitamin D deficiency had increased risk of being diagnosed with Schizophrenia in adult life. However, the exposure-risk relationship was non-linear...
DEC 12, 2018
Cell & Molecular Biology
DEC 12, 2018
Study Shows Why Diets Rich in Red Meat Increase Heart Disease Risk
For decades, we've known that red meat is a risk factor for heart disease. Now, researchers at the Cleveland Clinic know why....
Loading Comments...