New research from the University of Cincinnati shows early signs that light can be used as a treatment for certain diseases, including cancer.
Researchers from UC, the University of Illinois Urbana-Champaign and the University at Buffalo published the results of their study showing that light-activated proteins can help normalize dysfunction within cells in the journal Nature Communications on July 25.
Research results
Research focuses on the functions of mitochondria, organelles within a cell that act as the cell’s “powerhouse” and energy source. Organelles are small specialized structures that perform various jobs within cells.
Jiajie Diao, PhD, one of the authors of the study, said that hundreds of mitochondria are constantly coming together (a process called fusion) and dividing into smaller parts (a process called fission) to maintain balance in cells. healthy cells But when the mitochondria are not working properly, there is an imbalance of this process of fission and fusion.
This imbalance can lead to a number of mitochondrial diseases, including neurodegenerative diseases such as dementia and certain cancers.
Diao said that previous research found that another organelle inside cells called a lysosome may play a role in the fission of mitochondria. When a mitochondrion comes into contact with a lysosome, the lysosome can act like scissors and cut the mitochondria into smaller pieces.
Current research focused on initiating the fission process by linking lysosomes and mitochondria within cells. This was achieved using a technique known as optogenetics, which can precisely control specific cellular functions using light.
“Many proteins in plants are sensitive to light, telling plants whether it’s day or night. Optogenetics takes these light-sensitive proteins from plants and uses them in animal cells,” said Kai Zhang, PhD, associate professor at the University of Illinois at Urbana-Champaign. Champaign and co-author of the study, who developed the optogenetic tools to control mitochondria and lysosomes with blue light. “By attaching these proteins to organelles, light can be used to control the interaction between them, such as the mitochondria and lysosomes shown in this work,” he said.
The researchers connected two separate proteins to mitochondria and lysosomes inside stem cells. When stimulated by blue light, the proteins naturally bind together to form a new protein, which also brings the mitochondria and lysosome into contact. Once assembled, the lysosome can cut the mitochondria, achieving fission.
We found that it can restore mitochondrial function. Some of the cells may even return to normal. This shows that with just a simple light stimulation we can at least partially restore the cell’s mitochondrial function.”
Jiajie Diao, PhD, associate professor in the Department of Cancer Biology, UC School of Medicine and member of the University of Cincinnati Cancer Center
Diao said this technique could be especially useful for patients with very large mitochondria that need to be broken down into smaller pieces to achieve normal cellular function. The technique could also be targeted at cancer cells, continually breaking apart mitochondria into smaller and smaller pieces until they can no longer function.
“Eventually, cancer cells will kill themselves because mitochondria are their energy,” Diao said. “Without normal, functional mitochondria, all cancer cells will die.”
Because the proteins are activated by light, Diao said it allows for a more targeted approach to specific cells. Only cells exposed to the light are affected, meaning nearby healthy cells don’t have their mitochondria thrown out of balance by the technique.
There are currently other processes that can be used to induce mitochondrial fission, but Diao said the optogenetic method is safer as it does not involve any chemicals or toxic agents.
“What we have is actually the natural process, we’re just making it faster,” Diao said. “So it’s not like a chemical or a therapy or radiation therapy where you have to reduce the side effects.”
next steps
Diao said his team is already working to use the same technique to encourage fusion to address problems when mitochondria are out of balance because they’re too small and don’t come together as they should inside cells.
Further research from Zhang’s lab will also include developing new optogenetic systems that work with different colors of light, including green, red and infrared, since a longer wavelength will be needed to penetrate human tissue .
“We would like to further expand the toolbox by introducing multi-color optogenetic systems to give us multiple ways to control how organelles behave and interact,” Zhang said. “For example, one color causes the organelles to stick together, while the other forces them apart. This way, we can precisely control their interactions.”
Building on the current research with human stem cells, the team hopes to move forward to test its effectiveness using animal models on the way to testing the technique in humans through clinical trials. At the same time, Diao said other research groups are studying the use of magnetic fields and acoustic vibrations instead of light to achieve similar results.
Source:
Journal reference:
Qiu, K. et al. (2022) Light-activated mitochondrial fission by optogenetic control of mitochondria-lysosome contacts. Communications of nature. doi.org/10.1038/s41467-022-31970-5.