By Health and Science Africa
The UT Southwestern Medical Center has developed a new genetic technique that forces cells to rid themselves of mitochondria.
Their findings, published in Cell, is helping researchers to gain insight into the function of these critical organelles.
Phys.org reports that their findings, also add to fundamental knowledge about the role of mitochondria in cells and evolution and could eventually lead to new treatments for patients with mitochondrial diseases such as Leigh syndrome and Kearns-Sayre syndrome, which can affect numerous organ systems.
Jun Wu, Ph.D., Associate Professor of Molecular Biology at UT Southwestern said the new tool allows researchers to study how changes in mitochondrial abundance and the mitochondrial genome affect cells and organisms.
Dr. Wu co-led the study with Daniel Schmitz, Ph.D., a former graduate student in the Wu Lab and now a postdoctoral fellow at the University of California, Berkeley.
Mitochondria are organelles found in the cells of most eukaryotic organisms, including animals, plants, and fungi, whose cells contain a membrane-bound nucleus and other membrane-bound organelles.
They have their own genetic material, passed down exclusively through females of a species. They are thought to have originated as prokaryotic cells—which lack membrane-bound organelles—and to have invaded ancestral eukaryotic cells and formed a symbiotic relationship with them.
Researchers have long known that these organelles serve as cells’ powerhouses, generating the energetic molecule adenosine triphosphate that fuels all cellular operations. However, recent studies have shown mitochondria play direct roles in regulating cell death, differentiating stem cells into other cell types, transmitting molecular signals, aging, and developmental timing.
Although mitochondria appear to perform many of these roles through “crosstalk” with the DNA in a cell’s nucleus, how they perform this function—and what happens if this crosstalk ceases—has been unknown.
Dr. Wu, Dr. Schmitz, and their colleagues took advantage of a pathway called mitophagy that cells normally use to dispose of old or damaged mitochondria.
Using genetic engineering, the researchers forced cells to degrade all their mitochondria—a process known as “enforced mitophagy.”
The researchers used this process on human pluripotent stem cells (hPSCs), a type of cell typically formed early in development that can differentiate into other cell types.
Although this alteration caused the cells to stop dividing, the researchers unexpectedly found that the mitochondria-depleted cells could survive in petri dishes up to five days. They had similar results with different types of mouse stem cells and hPSCs harboring a pathogenic mitochondrial DNA mutation, suggesting enforced mitophagy can be a viable tool for depleting mitochondria across species and cell types.
The researchers also studied how depleting mitochondria might affect development in whole organisms.
They further said these results serve as starting points for new lines of research into the different roles mitochondria play in cellular function, tissues and organ development, aging, and species evolution. They plan to use enforced mitophagy to continue studying these organelles in a variety of capacities.
