All together now, say it with me: “The mitochondria is the powerhouse of the cell.” As a rite of passage for all students going through high school, the cell unifies all who had to go through any biology class. Of course, it is also one of the most crucial aspects of your body; understanding cell biology is pertinent to knowing what happens in internal processes like digestion, oxygen transport, and other metabolic processes. Of course, the cell is also key in many aspects of organisms, including genetics. It is thus important for scientists to understand what lies beneath the goo, and know what goes on inside the cell at a detailed level.
Researchers from the Center for Soft and Living Matter, in the Institute of Basic Science (IBS) in South Korea, are among many around the world in a constant search for determining the machinery that makes our cells tick. They took a particularly unique approach, though; they attempted to create artificial cell organelles—compartments within the cell that perform functions relevant to its survival, such as the nucleus and the endoplasmic reticulum—to gain a better understanding of how they work. In fact, they replicated what is perhaps the most famous (or infamous—depends on who you’re asking) of all organelles: the mitochondria. Their study was published in the journal Nature Catalysis.
The study in question made use of reprogrammed exosomes, or tiny bubble-like vesicles ,some 120 nm (nanometers) in diameter, that cells use to communicate with each other. They modified these exosomes by attaching a molecule called catechol to their surfaces, allowing these exosomes to fuse its surface membrane with another when exposed to metal ions like the iron (III) cation (Fe3+). They then inserted functional compounds and organic material into the exosomes prior to their fusion; in doing so, the exosomes merged both their membranes and their contents, allowing the two distinct functional compounds to interact and react with one another. Once the catechol molecules on the exosome surfaces bind to the Fe3+ ions in the surrounding solution, the exosomes themselves begin merging.
After initial testing of the success of their merger wherein they used a fluorescent chemical marker, the team then proceeded to preload the exosomes with reactants and enzymes, like glucose peroxidase (GOx) and horseradish peroxidase (HRP). Adding these functional components allowed the research team to test the new biocatalytic capabilities of their new fused exosomes, turning them into what the team called “biomimetic nanofactories.” The GOx-HRP pair formed what they called an enzyme system.
Afterwards, the team tried to check how well these new “nanofactories” can be internalized by actual, living cells. They tested this on cells obtained from human breast tissue, and their level of internalization was determined using chemical markers and microscopes. Here, they found that the exosomes were internalized primarily via endocytosis (which also happens to be a process in which some viruses enter our cells). Testing the enzyme system they implanted via exosomes revealed that the pair were still able to generate fluorescent products, even though they were already internalized by human cells.
Finally, the team implanted enzymes into the current GOx-HRP enzyme system that would allow them to produce adenosine triphosphate (ATP), the very chemical that provides energy to the cell—which also gives the organelle its famous (or, again, infamous) “powerhouse” moniker. Essentially, these fused exosomes became artificial mitochondria, capable of producing ATP even in the oxygen-deprived environment of solid spheroid tissue.
Corresponding author Cho Yoon-Kyoung notes that their new study “highlight[s] the potential of these exosomes as nanoreactors in regulating the metabolic activity of cells inside spheroids, and in attenuating cell damage due to hypoxia.” The team hopes that further research into this topic will open new avenues and ways of approaching disease treatment and biotechnology, among others.
References
- British Society for Cell Biology. (n.d.). Mitochondrion – much more than an energy converter [British Society for Cell Biology]. Retrieved September 29, 2021, from https://bscb.org/learning-resources/softcell-e-learning/mitochondrion-much-more-than-an-energy-converter/
- Institute of Basic Science. (2021, September 13). Scientists explore the creation of artificial organelles: Artificial organelles generated from Exosome fusion can function as energy reserves in the damaged tissues. ScienceDaily. https://www.sciencedaily.com/releases/2021/09/210913135624.htm
- Kumar, S., Karmacharya, M., Michael, I. J., Choi, Y., Kim, J., Kim, I., & Cho, Y.-K. (2021). Programmed exosome fusion for energy generation in living cells. Nature Catalysis, 1–12. https://doi.org/10.1038/s41929-021-00669-z
- Metabolism—Atp synthesis in mitochondria. (n.d.). Encyclopedia Britannica. Retrieved September 29, 2021, from https://www.britannica.com/science/metabolism
