New component in blood

Discovery could lead to improvements in treatment of diseases

| THE INDEPENDENT | Does the blood we thought to know so well contain elements that had been undetectable until now? The answer is yes, according to a team of researchers which has revealed the presence of whole functional mitochondria in the blood circulation. The discovery may deepen our knowledge of physiology and open up new avenues for treatment.

Researchers at the Montpellier Cancer Research Institute (IRCM) have discovered the new component in blood that has never been detected there before. Mitochondria are normally found inside cells, but the team has now discovered them floating around on their own in the bloodstream.

Often referred to as the power houses of cells, mitochondria are organelles; the tiny cellular structures that perform specific functions within a cell.  Mitochondria play a key role in metabolising; or processing the food, minerals and more that we consume into new cells, energy and waste products by means of chemical processes.  The new mitochondria revealed in blood are involved in metabolising energy and cell signaling. Occasionally they are found outside of cells, but usually only as fragments within the tiny disc-shaped cell fragments in blood called platelets.

After a seven-year study, an IRCM team has now found complete and fully-functioning mitochondria in blood plasma, contained inside highly-stable structures. Using electron microscopy, the researchers analyzed plasma samples from about 100 people, and found up to 3.7 million of these mitochondria-containing structures per milliliter of plasma.

The team was originally tipped off to the presence of mitochondria in blood by previous studies, which found that a person’s blood plasma can contain up to 50,000 times more mitochondrial DNA than other types of DNA. That implied that whole mitochondria were circulating through the bloodstream inside stable, protective structures.

“When we consider the sheer number of extracellular mitochondria found in the blood, we have to ask why such a discovery had not been made before,” says Alain Thierry, lead researcher on the study. “Our team has built up expertise in the specific and sensitive detection of DNA in the blood, by working on the fragmentation of extracellular DNA derived from the mitochondria in particular.”

The discovery means that this extracellular mitochondria must be playing some kind of biological role. The team hypothesises that it may be helping to induce immune and inflammatory responses, and helping cells communicate with each other.

Mitochondria are organelles that are found in the eukaryotic cells. A place of cellular respiration, they are the cells’ “batteries” and play a major role in energy metabolism and intercellular communication. Their particularity is to possess their own genome, transmitted solely by the mother and separate from the DNA contained in the nucleus. The mitochondria can sometimes be observed outside the cells in the form of fragments encapsulated within microvesicles. Under certain very specific conditions the platelets are also capable of releasing intact mitochondria into the extracellular space.

The work of a team led by Inserm researcher Alain R. Thierry at the Montpellier Cancer Research Institute (Inserm/Université de Montpellier/Montpellier Cancer Institute) has now revolutionised knowledge of this organelle by revealing that whole functioning extracellular mitochondria are in fact found in the bloodstream.

The researchers used previous findings which showed that the plasma of a healthy individual contains up to 50,000 times more mitochondrial DNA than nuclear DNA. They hypothesised that for it to be detectable and quantifiable in the blood in this manner, the mitochondrial DNA had to be protected by a structure of sufficient stability. In order to identify such a structure, plasma samples from around 100 individuals were analyzed.

This analysis revealed the presence in the blood circulation of highly stable structures containing whole mitochondrial genomes. Following examination of their size and density, as well as the integrity of their mitochondrial DNA, these structures observed using electron microscopy (up to 3.7 million per ml of plasma) were revealed to be intact and functional mitochondria.

Throughout the seven-year research period, the scientists used as many technical and methodological approaches as possible to validate this presence of circulating extracellular mitochondria in the blood.

But what is the role of these extracellular mitochondria? The answer to that could be linked to the structure of the mitochondrial DNA, similar to that of bacterial DNA, which gives it the ability to induce immune and inflammatory responses. Based on this observation, the researchers hypothesize that these circulating mitochondria could be implicated in many physiological and/or pathological processes requiring communication between the cells (such as the mechanisms of inflammation). Indeed, recent studies have demonstrated the ability of certain cells to transfer mitochondria between themselves, such as the stem cells with damaged cells. “The extracellular mitochondria could perform various tasks as messenger for the entire body,” Thierry explains.

In addition to its importance to our knowledge of physiology, this discovery could lead to improvements in the diagnosis, monitoring and treatment of certain diseases. In fact, the research team is now devoting its attention to evaluating the extracellular mitochondria as biomarkers in non-invasive prenatal diagnosis and cancer.