French biologists have found intact mitochondrial DNA molecules in blood plasma in particles the size of entire mitochondria, according to the FASEB Journal. Apparently, these are intact mitochondria, and they, like analogous organelles inside cells, are capable of reactions of the oxygen stage of cellular respiration.
In eukaryotes, DNA is normally contained inside cells and is surrounded by a membrane - nuclear or mitochondrial. If this molecule is in the cytoplasm or in the intercellular space, it is usually a sign of a viral infection or the death and fragmentation of a number of cells. Also, its sources are cancer cells and a number of others.
Usually, freely circulating DNA (as it is called in this case) is of nuclear origin and is associated with histone proteins that protect it from degradation. However, deoxyribonucleic acid from mitochondria can also be found outside of cells. Although in theory it degrades faster, since it is not protected by histones, it can be used as a marker of various diseases from breast cancer to ischemia of the heart muscle. In addition, a 2019 study showed that there is 50,000 times more free mitochondrial DNA in the blood of a healthy person than nuclear DNA.
Now biologists from the University of Montpellier (authors of the last mentioned article), led by Alain R. Thierry, using real-time polymerase chain reaction, estimated the number of free mitochondrial DNA molecules from the blood plasma of healthy people and patients with rectal cancer, as well as the length of its fragments.
In addition, scientists prepared blood samples for electron microscopy to assess the structure and size of particles floating in it. And the presence of mitochondria and their fragments in plasma was checked using a fluorescent dye that binds to mitochondrial proteins. The same was done for human rectal cancer cell cultures.
Left column: free mitochondria stained with a fluorescent dye. Right column: electron micrographs of mitochondria and their fragments from the same preparations. The first line is blood plasma, the second and third lines are rectal cancer cell cultures.
In both patients and healthy people, the average length of mitochondrial DNA fragments in blood plasma was close to that for an intact molecule. Most often, these DNAs were contained within membrane structures with an average diameter of 0.22 micrometers, which corresponds to the size of an entire mitochondrion. When researchers isolated these structures and determined their level of oxygen consumption, it turned out that it is quite large, which means that these organelles are quite capable of cellular respiration reactions.
The study did not test how long free mitochondria can exist in blood plasma. Why they are there in large quantities (from 0.2 to 3.7 million per milliliter of plasma) is not yet clear. The authors suggest that organelles can serve as a means of communication between cells. Perhaps their presence activates inflammation processes, but this does not explain the abundance of free mitochondria in the blood of healthy people.
Although mitochondria play a key role in cell respiration, some organisms can survive without them. Such, for example, are the protozoa from the Monocercomonoides group, which were found in the intestines of a chinchilla by colleagues of the authors of the corresponding article. And if the number of mitochondria is reduced in the culture of senescent cells or mouse liver, they will produce significantly less senescent (indicating aging) proteins.